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Practice Exams Exam - 2

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Practice Exams Exam - 2

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    Practice Exams Exam - 2 Practice Exams Exam - 2 Document Transcript

    • Practice Exams: Exam 2 CHAPTER 15 15-1 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.1 Nifedipine: Exam 2 Nifedipine (Procardia @) is a calcium channel blocker which specifically inhibits potential-dependent channels not receptor-operated channels, preventing calcium influx of cardiac and vascular smooth muscle (coronary, cerebral). Calcium channel blockers reduce myocardial contractility and A-V node conduction by reducing the slow inward cal- cium current. They are indicated in angina, cardiac dysrhythmias, and hypertension among others. Nifedipine appears to be metabolized entirely into an inactive metabolite, an acid and subsequently further metabolized to a lac- tone. Both the acid and the lactone are excreted into the urine and the feces. Hepatic blood flow in normals is 1.6 L/min Renal blood flow in normals is 1.2 L/min Echizen and Eichelbaum (Clin Pkin 1986; 11:425-49) and Kleinbloesem et al (Clin Pcol Therap 1986; 40: 21-8) reviewed the pharmacokinetics of Nifedipine. While the drug is not routinely given by IV bolus and does not strictly conform to a one compartment model, let's treat the data as if those problems can be ignored. The following data is offered for evaluation: TABLE 1-1. Nifedipine IV Bolus Profile Time (hr) Cp (mcg/L) Cm1 (mcg/L) Xm1f (mg) Xm1u (mg) Xm2f (mg) Xm2u (mg) 0.5 24.7 1 44.4 2 139 71.8 .14 .59 4 65.6 96.5 .44 1.83 .028 .11 6 31.1 100 .77 3.25 .073 .29 8 14.6 94.7 1.1 4.65 .135 .54 12 76.5 1.69 7.10 .291 1.15 24 34 2.77 11.63 .75 2.95 7 days 3.6 15.1 1.3 5.0 TABLE 1-2 Nifedipine Oral information Brand Generic Route IV Oral Capsule Oral Capsule 25 Dose (mg) 10 10 AUC (ug/L*hr) 785 236 204 AUMC (ug/L*hr2 ) 2093 866 816 15-2 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Nifedipine: Exam 2 15.1.1 NIFEDIPINE QUESTIONS: Find: 21) MRT (oral generic capsule) (hr) 22) MAT (oral generic capsule) (hr) 1) MRT iv (hr) 23) Ka, the apparent absorbtion rate con- 2) Ke (elimination rate constant) for Nife- stant, for the generic capsule (hr-1 ) dipine (hr-1 ) 24) Peak time for the generic capsule (hr) 3) T 1/2 for Nifedipine 25) Cpmax , the maximum concentration 4) Cp0 for iv dose (ug/L) of the generic oral capsule give as a single 5) Vd for Nifedipine (L) dose (ug/L) 7) Cp of Nifedipine at one hour after the 26) Comparative bioavailability of the oral IV dose capsules 8) AUC from 0 to one hour for the IV dose Your patient is controlled by 20 mg TID of the brand name oral capsule when he 9) Total Body Clearance of Nifedipine (L/ is healthy. hr) 27) What is his N for that dosing regimen? 10) Renal Clearance of Nifedipine (L/hr) 28) Cpssmax for this patient at this dosing 11) Hepatic Clearance of Nifedipine (L/hr) regimen (ug/L) 12) Renal Extraction Ratio 29) Cpssavg for this patient at this dosing 13) Hepatic Extraction Ratio regimen (ug/L) 14) Absolute bioavailability for the brand 30) Cpssmin for this patient at this dosing name capsule regimen (ug/L) 15) MRT (oral brand name capsule) (hr) You want to maintain his plasma con- 16) MAT (oral brand name capsule) (hr) centrations between 110% of Cpssmax and 90% of Cpssmin . How would you 17) Ka, the apparent absorbtion rate con- change the dosage regimen to if your stant, for the brand name capsule (hr-1 ) patient suffered from: 18) Peak time for the brand name capsule 31) stenosis of the kidney (Fr = 0.67). (hr) 32) renal failure (Fi = 0.67). 19) Cpmax , the maximum concentration of the brand name oral capsule give as a 33) stenosis of the liver (Fr = 0.67) single dose (ug/L) 34) cirrhosis of the liver (Fi = 0.67) 20) Absolute bioavailability for the generic capsule 15-3 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Nifedipine: Exam 2 TABLE 1-3 Nifedipine Answer Pool Small Medium Large Dosing changes: a) 0.00 a) 1.85 a) 59 a) 10 mg once daily b) 0.05 b) 2.67 b) 85 b) 10 mg BID c) 0.33 c) 3.67 c) 92.5 c) 10 mg TID d) 0.375 d) 4.0 d) 101 d) 10 mg QID e) 0.65 e) 4.32 e) 124 e) 20 mg once daily f) 0.75 f) 9.3 f) 147 f) 20 mg BID g) 0.85 g) 18.5 g) 185 g) 20 mg TID (no change necessary) h) 1.0 h) 32 h) 202 h) 20 mg QID i) 1.33 i) 38 i) 248 i) 30 mg once daily j) 1.57 j) 49 j) 294 j) 30 mg BID 15-4 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Nifedipine: Exam 2 15.1.2 NIFEDIPINE SOLUTIONS 21. Oral generic capsule MRT iv = 2.67hr 1. MRT = 4hr –1 k e = 0.375hr 2. 22. Oral generic capsule MAT = 1.33hr T1 ⁄ 2 = 1.85hr 3. 23. Oral generic capsule Cp 0 = 294ug ⁄ L 4. –1 Ka = 0.75hr Vd = 85L 5. 24. Oral generic capsule peak time 1.85hr 6. skip (error in numbering) 25. Oral generic capsule Cp 1 = 202ug ⁄ L 7. Cp max = 38ug ⁄ L AUC 0 – 1 = 248ug ⁄ L ⋅ hr 8. 26. Comparative bioavailability of the Cl s = 32L ⁄ hr oral capsules B/A: 9. AUC = 0.86 (ok) Cl r = 0 10. Peak time = 1.18 (ok) Cl h = 32L ⁄ hr 11. Cpmax = 0.78 (not ok!) N = 4.32 27. Er = 0 12. ss 185ug ⁄ L Cp max = 28. Eh = 0.33 13. ss 59ug ⁄ L 14. Absolute bioavailability for brand Cp ave = 29. name capsule = 0.75 ss 9.3ug ⁄ L Cp min = 30. 15. Oral brand name capsule MRT = 3.67hr 31. No change 16. Oral brand name capsule 32. No change MAT = 1.0hr 33. No change 17. Oral brand name capsule 34. No change –1 Ka = 1.0hr 18. Oral brand name peak time 1.57hr 19. Oral brand name Cp max = 49ug ⁄ L 20. Absolute bioavailability for generic = 0.65 15-5 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Valproate: Exam 2 15.2 Valproate: Exam 2 All questions are internally consistent. Information gained in any one can be used in all others. Note, however, there is a change in patient status midway through. Valproate is a carboxylic acid anticonvulsant. Its activity may be related, at least in part, to increase concentra- tions of the neurotransmitter inhibitor gamma aminobutyric acid in the brain. It is used alone or in combination with other anticonvulsants. in the prophylactic management of petit mal. It appears to be almost entirely cleared by liver function with negligible amounts excreted into the urine unchanged. It comes as soft gelatin capsules of 250 mg and enteric coated tablets 250 and 500 mg. The therapeutic range for valproate appears to be between 20 and 100 mic/ml. The volume of distribution is 0.19 L/Kg and your patient is 70 kg. TABLE 1-4 IV bolus Brand Generic Dose (mg) 500 250 250 AUC (mg/L*hr) 594 273 253 9428.6 4605.5 4184.6 2 AUMC(mg/L*hr ) 2.95 Tpeak (hr) Cpmax 14.35 Bioavailability (f) 1.0 .92 15-6 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Valproate: Exam 2 15.2.1 VALPROATE QUESTIONS 1) Calculate the MRTiv of Valproate (hr). a) 11 b) 15.87 c) 16.54 d) 16.87 e) 17.08 2) Calculate the rate constant of elimination (hr-1 ) in normals ? a) 0.091 b) 0.063 c) 0.060 d) 0.0593 e) 0.0585 3) Calculate the half life of Valproate (hr)? a) 7.6 b) 11 c) 11.5 d) 11.7 e) 11.8 4) Calculate the hepatic clearance of valproate (L/hr). a) 0.0084 b) 0.063 c) 0.84 d) 1.25 d) 2.5 5) Calculate the hepatic extraction ratio of valproate. a) 0.0063 b) 0.0084 c) 0.063 d) 0.084 e) 0.84 6) What is the maximum N for multiple dosing of Valproate? a) 0.78 b) 1.65 c) 2.12 d) 2.32 e) 2.5 7) What is the maximum acceptable dosing interval for normal patients (hr)? a) 8 b) 12 c) 18 d) 24 e) 25.5 8) What is the N if we are going to dose TID? a) 0.63 b) 0.727 c) 0.842 d) 1.25 e) 1.42 9) If you dosed this patient 500 mg BID with the brand name product, what would be your maximum concentration at steady state (mg/L)? a) 87.3 b) 70.9 c) 65.2 d) 52.8 e) 45.8 10) What would be your minimum concentration at steady state (mg/L)? a) 52.8 b) 32.7 c) 30.1 d) 27.1 e) 22.9 15-7 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Valproate: Exam 2 11) What would be your average concentration at steady state (mg/L)? a) 63.8 b) 49.8 c) 47.7 d) 45.8 e) 34.4 12) What loading dose would you give to get to Cpss right away (mg)? a) 250 b) 500 c) 750 d) 1000 e) 1500 13) If you changed the dosage regimen to 250 mg QID, what would happen to the Cpssmax, Cpssave, Cpssmin? a) Cpssmax - up, Cpssave - up, Cpssmin - up b) Cpssmax - down, Cpssave - down, Cpssmin - down c) Cpssmax - same, Cpssave - same, Cpssmin - same d) Cpssmax - up, Cpssave - same, Cpssmin - down e) Cpssmax - down, Cpssave - same, Cpssmin - up 14) Calculate f, the absolute bioavailability of the generic product. a) 0.67 b) 0.75 c) 0.85 d) 0.93e) 1.0 15) Calculate the comparative bioavailability of the generic product. a) 0.67 b) 0.75 c) 0.85 d) 0.93e) 1.0 16) Calculate the MRToral of the generic product. a) 11 b) 15.87 c) 16.54 d) 16.87 e) 17.08 17) Calculate the MAT of the generic product. a) 0.67 b) 0.75 c) 0.85 d) 0.93e) 1.0 18) Calculate the Ka of the generic product. a) 1.5 b) 1.33 c) 1.18 d) 1.08 e) 1.0 19) Calculate the peak time of the generic product. a) 2.21 b) 2.45 c) 2.59 d) 2.76 e) 2.95 20) Calculate the Cpmax of the generic product. 15-8 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Valproate: Exam 2 a) 8.1 b) 9.3 c) 10.7 d) 12.6 e) 14.4 21) Is the generic product bioequivalent? a) Yes b) No, because the comparative bioavailability is outside the federal guidelines. c) No, because the ratio of the peak times is outside the federal guidlines. d) No, because the ratio of the Cpmax s is outside the federal guidlines. e) No, because the generic fails more than one of the required comparisons. In patients who are also currently on phenobarbital their intrinsic clearance of valproate increases by 50% as the phe- nobarbital induces the enzymes which metabolize valproate. Further questions refer to this condition. 22) Calculate his new clearance. a) 0.0084 b) 0.063 c) 0.84 d) 1.25 d) 2.5 23) Calculate his new K. a) 0.095 b) 0.084 c) 0.063 d) 0.059 e) 0.042 24) Calculate his new maximum acceptable dosing interval (hr). a) 8 b) 12 c) 17 d) 18 e) 24 25) What dosage regimen would you recommend to try to maintain his plasma concentrations within 110% of the max- imum and 90% of the minimum concentrations attained when he was normal? a) 750 mg BID b) 500 mg TID c) 750 mg TID d) 250 mg QID e) 500 mg QID 15-9 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Valproate: Exam 2 15.2.2 VALPROATE SOLUTIONS 15-10 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Methyl phenidate 15.3 Methyl phenidate Methyl phenidate (MP) (Ritalin@) is an effective stimulant in the treatment of narcolepsy in adults and attention deficit syndrome in children. It is entirely metabolized to the inactive metabolite, Ritalinic Acid (RA), by the liver which is subsequently excreted unchanged into the urine. The following information was obtained from a 70 Kg male. QH = 24 mL/min/Kg QR = 19 mL/min/Kg TABLE 1-5 Ritalin Data Brand IV Name Generic Dose (mg) 10 20 20 AUC (ug/ml*hr) 0.20 0.04 0.035 0.32 0.14 0.1225 AUMC (ug/ml*hr2 TABLE 1-6 Ritalin Answer Pool Itty- Bitty Tiny Puny Small Medium Large Words a 0 0.016 0.1 1.1 10 100 yes b 0.00016 0.0251 0.125 1.6 20 125 no, Ratio of Tps c 0.0005 0.035 0.25 1.75 30 225 no, Ratio of Cmaxs d 0.00074 0.042 0.35 1.9 40 375 no, Ratio of AUCs e 0.00084 0.05 0.42 2.6 50 435 no, Ratio of AUMCs f 0.0016 0.067 0.53 3.5 60 550 no, more than one criterion g 0.005 0.075 0.625 4.2 70 675 20 mg TID h 0.0074 0.0875 0.727 5.0 80 750 20 mg BID i 0.0084 0.091 0.875 7.27 90 875 20 mg QD j 0.0090 0.096 0.91 8.75 96 995 20 mg QID 15-11 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Methyl phenidate 15.3.1 METHYL PHENIDATE QUESTIONS: 1) MRT iv (hr) 25) Cpmax , the maximum concentration of the generic oral tablet give as a single dose 2) Ke (elimination rate constant) for (ug/mL) Ritalin (hr-1 ) 26) Comparative bioavailability of the oral 3) T 1/2 for Ritalin (hr) tablets 4) Cp0 for iv dose (ug/mL) 27) Are the tablets bioequivalent? 5) Vd for Ritalin (L) Your patient is controlled by 20 mg TID of 6) Cp of Ritalin at one hour after the IV the brand name oral tablet when he is dose healthy. For This patient and this dosage regimen, what is his: 7) AUC from 0 to one hour for the IV dose 28) N ? 8) Total Body Clearance of Ritalin (L/hr) 29) Cpssmax (ug/mL) 9) Renal Clearance of Ritalin (L/hr) 30) Cpssavg (ug/mL) 10) Hepatic Clearance of Ritalin (L/hr) 31) Cpssmin (ug/mL) 11) Intrinsic Hepatic Clearance of Ritalin (L/hr) You want to maintain his plasma concen- trations between 110% of Cpssmax and 90% of 12) Renal Extraction Ratio Cpssmin . How would you change the dosage 13) Hepatic Extraction Ratio regimen to if your patient suffered from: 14) Absolute bioavailability for the brand (in no case was there a change in Vd) name tablet 32) stenosis of the kidney (Fr = 0.67)? 15) MRT (oral brand name tablet) (hr) 33) renal failure (Fi = 0.34)? 16) MAT (oral brand name tablet) (hr) 34) stenosis of the liver (Fr = 0.67)? 17) Ka, the apparent absorbtion rate con- 35) cirrhosis of the liver. (Fi = 0.67)? stant, for the brand name tablet (hr-1 ) 36) treatment with phenobarbital (Fi = 18) Peak time for the brand name tablet 1.33)? (hr) 19) Cpmax , the maximum concentration of the brand name oral tablet give as a single dose (ug/mL) 20) Absolute bioavailability for the generic tablet 21) MRT (oral generic tablet) (hr) 22) MAT (oral generic tablet) (hr) 23) Ka, the apparent absorbtion rate con- stant, for the generic tablet (hr-1 ) 24) Peak time for the generic tablet (hr) 15-12 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Methyl phenidate 15.3.2 METHYL PHENIDATE SOLUTIONS: 19. Brand name - MRT iv = 1.6hr 1. Cp max = 0.0084ug ⁄ mL –1 k = 0.625hr 2. Generic - f = 0.0875 20. T1 ⁄ 2 = 1.1hr 3. Generic - MRT = 3.5hr 21. Cp 0 = 0.125ug ⁄ mL 4. Generic - MAT = 1.9hr 22. Vd = 80L 5. –1 Generic - Ka = 0.53hr 23. Cp 1 = 0.067ug ⁄ mL 6. Generic - T peak = 1.75hr 24. 7. 25. Generic - AUC 0 – 1 = 0.096ug ⁄ mL ⋅ hr Cp max = 0.0074ug ⁄ mL Cl s = 50L ⁄ hr 8. 26. Comparative bioavailability = 0.875 Cl r = 0 9. 27. Yes, the tablets are bioequivalent - Cl h = 50L ⁄ hr all parameters are within federal guide- 10. lines. Cl int = 100L ⁄ hr 11. N = 7.27 28. Er = 0 12. ss 0.0251ug ⁄ mL Cp max = 29. Eh = 0.53 13. ss 0.005ug ⁄ mL Cp avg = 30. Brand name - f = 0.1 14. ss 0.00016ug ⁄ mL Cp min = 31. Brand name - MRT = 3.5hr 15. 32. 20 mg TID Brand name - MAT = 1.9hr 16. 33. 20 mg TID –1 34. 20 mg BID Brand name - Ka = 0.526hr 17. 35. 20 mg TID Brand name - Tpeak = 1.74hr 18. 36. 20 mg QID 15-13 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15-14 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Verapamil 15.4 Verapamil Verapamil is a calcium channel blocker with vasodilatory and antiarrhythmic effects. It is about 95% metabolized by the liver with the metabolites showing up in the urine and feces. Hepatic blood flow in normals is 1.6 L/min Renal blood flow in normals is 1.2 L/min TABLE 1-7 Verapamil Data Brand Generic Route IV Oral Tablet Oral Tablet Dose (mg) 15 80 80 AUC (ng/mL*hr) 300 480 400 AUMC (ng/mL*hr2 ) 1600 2690 2280 Verapamil Answer Pool TABLE 1-8 Dosing regimens Bioavailability answers Tiny Small Medium Large a 0 1.06 26 116 40 mg qd Yes b 0.063 2.15 46 267 40 mf bid No, tp ratio is not within limits c 0.188 2.50 47.5 369 40 mg tid No, Cpmax ratio is not within limits d 0.250 2.70 50 533 40 mg qid No, AUC ratio is not within limits e 0.270 3.69 56 637 80 mg qd No, f ratio is not within limits f 0.300 5.33 61.5 830 80 mg bid No, ka ratio is not within limits g 0.370 5.60 76.5 905 80 mg tid No, ke ratio is not within limits h 0.693 5.70 83 970 80 mg qid No, MRT ratio is not within limits i 0.85 6.37 90.5 1160 160 mg qd No, Cl ratio is not within limits j 0.905 8.30 97 2670 160 mg bid No, more than one of the required ratios are no within limits 15-15 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Verapamil 15.4.1 VERAPAMIL QUESTIONS 1) MRT iv (hr) 23) Ka, the apparent absorbtion rate con- stant, for the generic tablet (hr-1 ) 2) Ke (elimination rate constant) for Vera- pamil (hr-1 ) 24) Peak time for the generic tablet (hr) 3) T 1/2 for Verapamil 25) Cpmax , the maximum concentration of the generic oral tablet give as a single 4) Cp0 for iv dose (ug/L) dose (ug/L) 5) Vd for Verapamil (L) 26) Comparative bioavailability of the oral 7) Cp of Verapamil at one hour after the IV tablets dose 27) Are the tablets bioequivalent? 8) AUC from 0 to one hour for the IV dose Your patient is controlled by 80 mg TID 9) Total Body Clearance of Verapamil (L/ of the brand name oral tablet when he is hr) healthy. 10) Renal Clearance of Verapamil (L/hr) 28) What is his N for that dosing regimen? 11) Hepatic Clearance of Verapamil (L/hr) 29) Cpssmax for this patient at this dosing regimen (ug/L) 12) Renal Extraction Ratio 30) Cpssavg for this patient at this dosing 13) Hepatic Extraction Ratio regimen (ug/L) 14) Absolute bioavailability for the brand 31) Cpssmin for this patient at this dosing name tablet regimen (ug/L) 15) MRT (oral brand name tablet) (hr) You want to maintain his plasma con- 16) MAT (oral brand name tablet) (hr) centrations between 110% of Cpssmax and 90% of Cpssmin . How would you 17) Ka, the apparent absorbtion rate con- change the dosage regimen to if your stant, for the brand name tablet (hr-1 ) patient suffered from: 18) Peak time for the brand name tablet 32) stenosis of the kidney (Fr = 0.67). (No (hr) change in volume of distribution.) 19) Cpmax , the maximum concentration 33) renal failure (Fi = 0.34).(Volume of of the brand name oral tablet give as a sin- distribution is reduced in this disease to gle dose (ug/L) 50% of normal) 20) Absolute bioavailability for the generic 34) stenosis of the liver (Fr = 0.67) (No tablet change in volume of distribution) 21) MRT (oral generic tablet) (hr) 35) cirrhosis of the liver (Volume of Dis- 22) MAT (oral generic tablet) (hr) tribution and the bioavailability are both doubled while the half life is quadrupled ) 15-16 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Verapamil 15.4.2 VERAPAMIL SOLUTIONS 17. Brand name tablet - MRT iv = 5.33hr 1. –1 Ka = 3.69hr –1 k e = 0.188hr 2. 18. Brand name tablet - peak time - 0.85hr T1 ⁄ 2 = 3.69hr 3. 19. Brand name tablet - Cp 0 = 56ug ⁄ L 4. Cp max = 76.5ug ⁄ L Vd = 267L 5. 20. Generic - Absolute bioavailability - f = 0.25 6. skip - error in numbering Cp 1 = 47ug ⁄ L 7. Generic - MRT = 5.7hr 21. AUC 0 – 1 = 50ug ⁄ L ⋅ hr Generic - MAT = 0.37hr 22. 8. –1 Cl = 50L ⁄ hr Generic - Ka = 2.70hr 9. 23. Cl r = 2.50L ⁄ hr Generic - T peak = 1.06hr 10. 24. Cl h = 47.5L ⁄ hr Generic - Cp max = 61.5ug ⁄ L 11. 25. 26. Comparative bioavailability - 0.85 Er = 0.063 12. 27. The tablets are not bioequivalent - Eh = 0.49 13. Correction - should peak time ratio is not within limits. be added to answer pool N = 2.15 28. 14. Brand name tablet - absolute bio- ss 116ug ⁄ L availability = 0.30 Cp max = 29. 15. Brand name tablet - ss Cp avg = 60ug ⁄ L (change in 30. MRT = 5.60hr answer pool) 16. Brand name tablet - ss 26ug ⁄ L MAT = 0.270hr Cp min = 31. 32. No change in dosing regimen - 80 mg TID 15-17 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Verapamil 33. 40 mg TID 35. 40 mg BID 34. No change in dosing regimen - 80 mg TID 15-18 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Hydromorphone hydrochloride 15.5 Hydromorphone hydrochloride Hydromorphone hydrochloride is an analog of morphine which has about seven times the analgesic effect of morphine when given by IV. It is about 90% metabolized. The following data was obtained by Valner et al J.Clin Pcol 21(1981) 152-6: TABLE 1-9 Hydromorphone hydrochloride Data Oral tablet Oral tablet IV Brand Generic Dose (mg) 2 4 4 AUC (ng/mL*hr) 83 87 65 AUMC (ng/mL*hr2 ) 291 348 292 15-19 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Hydromorphone hydrochloride 15.5.1 HYDROMORPHONE HYDROCHLORIDE QUESTIONS For the IV product, find: MRTiv. (291/83=3.5) R(Bio)= 0.75 fail 1. 27. You would like to dose your healthy K. (1/3.5=0.285 2. patient using the brand name tablet so T1/2 (0.693/.285= 2.4 hr) 3. that his plasma concentration is in the Cp0 (AUC*K = 83*0.285= 23.7ng/mL 4. therapeutic range of 35 to 5 ng/mL. Ku (0.1*0.285=0.029) 5. Find: Km (0.9*0.285=0.256) 6. Nmax (ln(35/5)/ln(2) = 2.8 28. Cls (f*D/AUC=1*2000/83=24L/hr) 7. Taumax (2.8*2.4=6.74 hr 29. Vd (Cls/K=Vd= 24/0.285=84L 8. Maximum acceptable tau = 6 30. Clh (0.9*Cls = 21.6 L/hr 9. N (6/2.4 =2.5) 31. Clr (0.1*Cls = 2.4 L/hr 10. What dosage regimen would you recom- 32. Eh (21.6 / (24 mL/min * 60 min * 70 Kg / 11. mend? (4mg q6h) 1000mL/L) = 0.2 Cpssmax? (30 ng/mL) 33. Er ( 2.4 / ( 10 ml/min * 60 min * 70 Kg / 12. Cpssavg? (14 ng/mL) 34. 1000mL/L) = 0.06 Cpssmin? ( 5 ng/mL) 35. For the Brand name oral tablet, find: He gets renal stenosis (Fr = 0.5) with no MRT (348/87=4.0) 13. change in Vd. Find: MAT(4 - 3.5 = 0.5) 14. FClr0.94 36. Ka (1/0.5 = 2.0) 15. Clr*2.3 37. Tp (ln(ka/K)/(ka-K)=1.95/1.715=1.14hr 16. FClh1 38. Absolute bioavailability, f ((87/4)/(83/ 17. Clh*21.6 39. 2)=0.52 FCls.99 40. Cpmax (18 ng/mL) 18. Cls*23.9 41. K*0.284 42. For the Generic oral tablet, find: t1/2*2.44 43. MRT ( 292/65=4.5 hr) 19. Nmax 2.8 44. MAT (4.5 - 3.5 = 1 hr) 20. Taumax6.83 45. ka (1/MAT = 1/1=1 hr-1) 21. Maximum acceptable tau 6 46. Tp (ln(1/0.285)/(1-0.285)=1.26/.715=1.76 22. N 2.46 47. hr What dosage regimen would you recom- 48. Absolute bioavailability, f ((65/4)/(83/ 23. mend? 4mg q6h 2)=0.39 Cpssmax? 30 49. Cpmax (11 ng/mL) 24. Cpssavg? 15 50. Cpssmin? 5.5 51. Would you consider the oral tablets to be bioequivalent? Why or why not? His stenosis of the kidney clears and he No R(Tp) = 1.54 fail 25. now goes into renal dysfunction R(Cp) = 0.61 fail 26. (Fi=0.5), find: 15-20 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Hydromorphone hydrochloride FClr.52 Taumax8 52. 77. Clr*1.23 Maximum acceptable tau 8 53. 78. FClh2 N6 54. 79. Clh*21.6 What dosage regimen would you recom- 55. 80. mend? 4 mg q6h FCls.95 56. Cpssmax? 32 81. Cls*22.8 57. Cpssavg? 17 82. K*0.271 58. Cpssmin? 7.5 83. t1/2*2.55 59. Nmax 2.8 60. His stenosis of the liver clears and he Taumax 7.13 61. now suffers from liver dysfunction Maximum acceptable tau6 62. (Fi=0.05), Find: N 2.35 63. FClr1 84. What dosage regimen would you recom- 64. mend? 4mg q6h Clr*2.4 85. Cpssmax? 31 FClh.56 65. 86. Cpssavg? 15 Clh*12 66. 87. Cpssmin? 6.1 FCls.6 67. 88. Cls*14.4 89. K*.171 His renal dysfunction clears and now he 90. suffers from stenosis of the liver t1/2*4.04 91. (Fr=0.5), Find: Nmax 2.8 92. FClr1 Taumax11.3 68. 93. Clr*2.4 Maximum acceptable tau8 69. 94. FClh.833 N 1.48 70. 95. Clh*18 What dosage regimen would you recom- 71. 96. mend?4 mg q8h FCls.85 72. Cpssmax? 33 97. Cls*20.4 73. Cpssavg? 18 98. K*.243 74. Cpssmin?8.4 99. t1/2*2.85 75. Nmax 2.8 76. 15-21 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Hydromorphone hydrochloride 15-22 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.6 Fosinopril Sodium Fosinopril Sodium (MW 585) is a phosphinic prodrug of the angiotensin converting enzyme (ACE) inhibitor fosinopri- lat (MW 563). After oral administration, fosinopril is slowly and incompletely absorbed, and is converted to the active fosinoprolat by esterases in the gastrointestinal mucosa and the liver. Unlike other ACE inhibitors, elimination of fosi- noprilat is divided equally between renal and hepatic pathways. With the IV dose fosinoprilat was given and mea- sured. With the oral dose fosinopril was given but fosinoprilat was measured. The following information was obtained from a 70 Kg male. This information was constructed from Kostis et al “Fosinopril: Pharmacokinetics and pharmaco- dynamics in congestive heart failure” Clin Pcol Ther 58(6) 660-5 (1995); Hui et al “Pharmacokinetics of fosinopril in patients with various degrees of renal function” Clin Pcol Ther 49(4) 457 -66 (1991) QH = 24 mL/min/Kg Blood QR = 19 mL/min/Kg Blood TABLE 1-10 Fosinopril Data IV Brand Name Generic Tablet Tablet Dose (mg) 7.5 10 10 AUC (ng/ml*hr) 5700 1500 1400 AUMC (ng/ml*hr2) 78000 25000 23100 TABLE 1-11 Fosinopril Answer Pool: a 0 0.015 0.19 1.3 10 100 yes b 0.00016 0.0251 0.21 1.6 13.7 142 no, Ratio of Tps c 0.0005 0.035 0.25 1.75 16.6 192 no, Ratio of Cmaxs d 0.00074 0.042 0.36 1.9 18 253 no, Ratio of AUCs e 0.00084 0.05 0.42 2.8 50 387 no, Ratio of AUMCs f 0.0016 0.067 0.53 3.5 67 402 no, more than one criterion g 0.005 0.073 0.65 4.0 73 416 10 mg qid h 0.0064 0.0875 0.72 5.6 84 750 10 mg tid i 0.0084 0.091 0.84 7.0 93 875 10 mg bid j 0.0090 0.096 0.93 9.5 96 995 10 mg qd 15-23 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.6.1 FOSINOPRIL QUESTIONS 1) MRT for fosinoprilat (hr) 2) Ke for fosinoprilat (hr-1) 3) T ? for Fosinoprilat (hr) 4) Cp0 for iv dose (ng/mL) 5) Vd for Fosinoprilat (L) 6) Cp of Fosinoprilat at one hour after the IV dose 7) AUC from 0 to one hour for the IV dose 8) Total Body Clearance of Fosinoprilat (L/hr) 9) Renal Clearance of Fosinoprilat (L/hr) 10) Hepatic Clearance of Fosinoprilat (L/hr) 11) Intrinsic Hepatic Clearance of Fosinoprilat (L/hr) 12) Renal Extraction Ratio 13) Hepatic Extraction Ratio 14) Absolute bioavailability for the brand name tablet 15) MRT (oral brand name tablet) (hr) 16) MAT (oral brand name tablet) (hr) 17) Ka, the apparent absorption rate constant, for the brand name tablet (hr-1 ) 18) Peak time for the brand name tablet (hr) 19) Cpmax , the maximum concentration of the brand name oral tablet give as a single dose (ng/mL) 20) Absolute bioavailability for the generic tablet 21) MRT (oral generic tablet) (hr) 22) MAT (oral generic tablet) (hr) 23) Ka, the apparent absorption rate constant, for the generic tablet (hr-1 ) 24) Peak time for the generic tablet (hr) 25) Cpmax , the maximum concentration of the generic oral tablet give as a single dose (ng/mL) 26) Comparative bioavailability of the oral tablets 27) Are the tablets bioequivalent? Your patient is controlled by 10 mg TID of the brand name oral tablet when he is healthy. For This patient and this dosage regimen, what is his: 28) N ? 15-24 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 29) Cpssmax (ng/mL) 30) Cpssavg (ng/mL) 31) Cpssmin (ng/mL) You want to maintain his plasma concentrations between 120% of Cpssmax and 80% of Cpssmin . How would you change the dosage regimen to if your patient suffered from: (in no case was there a change in Vd) 32) stenosis of the kidney (Fr = 0.67)? 33) renal failure (Fi = 0.34)? 34) stenosis of the liver (Fr = 0.67)? 35) cirrhosis of the liver. (Fi = 0.67)? 36) treatment with phenobarbital (Fi = 1.5)? 15-25 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 : Fosinopril Sodium 15.6.2 FOSINOPRIL SODIUM SOLUTIONS 19. Oral brand name tablet MRT = 13.7hr 1. Cp max = 0.073ng ⁄ mL –1 k = 0.073hr 2. 20. Oral generic tablet absolute bio- availability is 0.19 T1 ⁄ 2 = 9.5hr 3. 21. Oral generic tablet Cp 0 = 416ng ⁄ mL 4. MRT = 16.6hr Vd = 18L 5. 22. Oral generic tablet MAT = 2.8hr Cp 1 = 387ng ⁄ mL 6. –1 AUC 0 – 1 = 402ng ⁄ mL Generic tablet Ka = 0.36hr 23. 7. Generic tablet peak time 5.6hr 24. Cl s = 1.3L ⁄ hr 8. 25. Generic tablet Cl r = 0.65L ⁄ hr Cp max = 0.067ng ⁄ mL 9. Cl h = 0.65L ⁄ hr 10. 26. Comparative bioavailability of the oral tablets = 0.93 11. Intrinsic Hepatic Clearance is 27. Yes! the tablets are bioequivalent 0.65L ⁄ hr The AUCs, peak times, and Cp max s are Er = 0.015 12. all within 20% range. N = 0.84 Eh = 0.0064 28. 13. ss 253ng ⁄ mL 14. Oral brand name tablet absolute Cp max = 29. bioavailability is 0.21 ss 192ng ⁄ mL Cp avg = 15. Oral brand name tablet 30. MRT = 16.6hr ss 142ng ⁄ mL Cp min = 31. 16. Oral brand name tablet 32. 10 mg TID MAT = 2.8hr 33. 10 mg BID 17. Oral brand name tablet 34. 10 mg TID –1 Ka = 0.36hr 35. 10 mg TID 18. Oral brand name tablet peak time 36. 10 mg QID 5.6hr 15-26 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15-27 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.7 Remoxipride Remoxipride (MW 296 - Unionized Base pKa 9.4) is a new antipsychotic of the benzamide type (See figure 1). The pharmacokinetics were studied by Movin-Osswald and Hammarlind-Udenaes (Brit. J Clin Pcol 1991 32(3) 355ff). Their results are summarized in table 1. The HCl salt of the drug was given (MW 332.5) to these patients in this study but the drug concentration was reported as the free base in the plasma. In this study, 25% of the Remoxipride was excreted unchanged, 75% was metabolized. The hepatic and renal blood flow in these patients was 1.5 and 1.2 L/min respectively. REMEMBER TO PAY ATTENTION TO UNITS. Remoxipride FIGURE 4-5. TABLE 1-12 Remoxipride Data IV bolus Oral Solution Tablet A Tablet B Dose (mg) 50 100 100 AUMC (umole/ 145 158.7 319.6 282.6 L*hr2 ) AUC (umole/L*hr) 20.9 19.8 37.6 31.4 Tp (hr) 3.6 Cpmax (mg/L) .8 f .75 15-28 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.7.1 REMOXIPRIDE QUESTIONS 1) Find the MRT of the IV product (hr). 2) Find the elimination rate constant of remoxipride (hr-1 ). 3) Find the Cp0 of the IV product (mg/L) 4) Find the volume of distribution of the IV product. (L) 5) Find the half life of remoxipride (hr). 6) Find the clearance of remoxipride (L/hr). 7) Find the renal clearance (L/hr). 8) Find the hepatic clearance 9) Find the renal extraction ratio. 10) Find the hepatic extraction ratio. 11) Find the MRT of remoxipride given as the oral solution (hr). 12) Find the MAT of remoxipride given as oral solution (hr). 13) Find the absorption rate constant of remoxipride given as an oral solution (hr-1 ). 14) Find the bioavailability of the oral solution (f). 15) Find the peak time of the oral solution (hr). 16) Find the MRT of remoxipride given as Tablet A, the brand name product. 17) Find the MAT of remoxipride given as Tablet A. 18) Find the apparent absorption rate constant (ka) of remoxipride given as Tablet A. 19) Find the peak time of Tablet A. 20) Find the single dose Cpmax for tablet A (mg/L) 21) Find the mean dissolution time (MDT) of Tablet A, the brand name product (hr). 22) Is Tablet B, the generic product is bioequivalent to Tablet A. Why or why not? 23) Find N for BID dosing. 24) Find Cpss max for two caps bid for the brand name product. 25) Find Cpss avg for two caps bid for the brand name product. 26) Find Cpss min for two caps bid for the brand name product. 27) Which change in physiological status would result in the most significant change in the TBC of remoxipride? a) Changes which effect the flow of blood to the liver. b) Changes which effect the flow of blood to the kidney. c) Changes which effect the function of the liver. 15-29 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 d) Changes which effect the function of the kidney. Your patient is experiencing that change. That physiological function was up 75% above normal (F = 1.75). 28) Find his new renal clearance 29) Find his new hepatic clearance. 30) Find his new total body clearance. 31) Assuming now change in volume of distribution, find his new half life. 32 Assuming no change in dosage regimen, find his new N. 33 What dosing regimen would you recommend to return his plasma concentrations back to normal (within 110% of max and 90% of min)? 15-30 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.7.2 REMOXIPRIDE SOLUTIONS MRT = 6.93hr 1. –1 k e = 0.144hr 2. Cp 0 = 0.88mg ⁄ L 3. Vd = 50L 4. T1 ⁄ 2 = 4.8hr 5. Cl = 7.28L ⁄ hr 6. Cl r = 1.8L ⁄ hr 7. Cl h = 5.46L ⁄ hr 8. Er = 0.025 9. Eh = 0.06 10. Oral solution MRT = 8hr 11. Oral solution MAT = 1.07hr 12. –1 Oral solution Ka = 0.935hr 13. Oral solution bioavailability f = 0.95 14. Oral solution peak time 2.4hr 15. Tablet A MRT = 8.5hr 16. Tablet A MAT = 1.57hr 17. –1 Tablet A Ka = 0.637hr 18. Tablet A peak time 3.0hr 19. Tablet A single dose Cp max = 1.03mg ⁄ L 20. Tablet A MDT = 0.5hr 21. Tablet B is not bioequivalent to Tablet A because peak time and Cp max are out of 22. federal guidelines. For dosing BID, N = 2.5 23. 15-31 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 ss 3.88mg ⁄ L Cp max = 24. ss 1.85mg ⁄ L Cp avg = 25. ss 0.685mg ⁄ L Cp min = 26. 27. The change in physiological status that would result in the most significant change in TBC of remoxipride is (C) - changes which effect the function of the liver. 28. New renal clearance = no change New Cl h = 9.0L ⁄ hr 29. New Cl s = 10.8L ⁄ hr 30. New T1 ⁄ 2 = 3.2hr 31. New N = 3.75 32. 33. The dosing regimen to recommend = 200 mg TID 15-32 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.8 Naproxen Naprosyn@ (naproxen) is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic properties. It is well absorbed (f = 0.95) and highly protein bound (98%) with a volume of distribution of about 10 L and a half-life of 13 hours in normal adults. It is almost entirely cleared by hepatic function (CLr = 1%) with about one- third being metabolized to the 6-o-desmethylnaproxen (which is further metabo- lized by conjugation) and two-thirds being conjugated directly. Both the 6-o-des- methyl metabolites as well as the conjugates are inactive. Normal dosing is 500 mg Naproxen BID. You stock 200 and 500 mg tablets in your HMO. For the following conditions, new parameters are given in parentheses. Concomitant treatment with Probenecid, a uricosuric which increases the urinary excretion of uric acid, while not interfering with the protein binding, effectively blocks the hepatic conjugation process reducing the hepatic function (Clinth ) to one-third of normal. In chronic renal failure (Fir = 0.1) the protein binding is reduced (94%) because of uremia. This results in a marginal increase in half-life (14 hr.) In rheumatoid arthritis, hypoalbuminaemia results in a reduction in protein binding (97%) and increase in the volume of distribution (13 L). Elderly patients exhibit a decrease in binding (96%), but no change in half-life or volume of distribution. For each of the conditions, (with Probenecid, chronic renal failure, arthritic, and elderly), please recommend a dosage regimen which would give approximately the same plasma concentrations of free naproxen obtained in the normal case (+ 10%.) Constants: Q r = 0.0191 ------------------- renal blood perfusion ⋅ 70kg ⋅ 60min ≈ 80 -----blood L- L --------- min ⋅ kg hr hr L min L Q H = 0.0238 ------------------- hepatic blood perfusion ⋅ 70kg ⋅ 60--------- ≈ 100 -----blood - min ⋅ kg hr hr Extraction ratios are calculated for normals and considered to be constant through- out. 15-33 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.8.1 NAPROXEN QUESTIONS TABLE 1-1. Question Numbers For Exam Patient Condition Normal Probenecid Chronic Rheumatoid Elderly treatment Renal Failure arthritis 1 27 51 75 99 Dose(mg) 2 28 52 76 100 f 3 29 53 77 101 fu 4 30 54 78 102 Vd (L) 5 31 55 79 103 k (hr-1) 6 32 56 80 104 T 1/2 (hr) 7 33 57 81 105 AUC (mg/L*hr) 8 34 58 82 106 % Cl h 9 35 59 83 107 % Cl r 10 36 60 84 108 Cl tot (L/hr) 11 37 61 85 109 Cl h (L/hr) 12 38 62 86 110 Cl r (L/hr) 13 Eh 14 Er 15 39 63 87 111 (L/hr) Cl h int 16 40 64 88 112 (L/hr) Cl r int 17 41 65 89 113 FR h 18 42 66 90 114 FI h 19 43 67 91 115 FR r 20 44 68 92 116 FI r 21 45 69 93 117 FCL τ (hr) 22 46 70 94 118 23 47 71 95 119 N 24 48 72 96 120 µg ss  ------- Cp -  mL max free 15-34 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 25 49 73 97 121 ss  µg  Cp ------- - avg free  mL 26 50 74 98 122 µg ss  ------- Cp -  mL min free Answer Pool S M L XL XXL XXXL A 0.000067 0.0182 0.100 1.0 10.0 100 B 0.0005 0.0200 0.133 1.1 11.3 200 C 0.0050 0.0300 0.177 1.4 12.0 303 D 0.0080 0.0400 0.182 1.5 13.0 356 E 0.0089 0.0495 0.267 1.6 13.3 500 F 0.0092 0.0533 0.315 1.7 14.0 595 G 0.0095 0.0600 0.333 1.8 26.5 891 H 0.0097 0.0610 0.341 1.9 31.7 1044 I 0.0098 0.0675 0.528 2.0 38.1 2000 J 0.0099 0.0700 0.533 2.1 45.0 3000 A 0.0790 0.577 2.2 50.0 B 0.0798 0.615 2.9 53.0 C 0.0857 0.675 3.0 62.0 D 0.0923 0.700 5.3 80.0 E 0.0950 0.790 6.2 86.0 F 0.0970 0.798 8.0 92.0 G 0.0990 0.857 8.5 97.0 I 0.0999 0.923 9.0 99.0 J 0.09997 0.95 9.9 99.97 15-35 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.8.2 NAPROXEN SOLUTIONS TABLE 1-1. Question Numbers For Exam Patient Condition Normal Probenecid Chronic Rheumatoid Elderly treatment Renal Failure arthritis 1. 500 mg 27. 200 51. 500 75. 500 99. 200 Dose(mg) 2. 0.95 28. 0.95 52. 0.95 76. 0.95 100. 0.95 f 3. 0.02 29. 0.02 53. 0.06 77. 0.03 101. 0.04 fu 4. 10 30. 10 54. 31.67 78. 13 102. 10 Vd (L) 5. 0.0533 31. 0.0182 55. 0.0495 79. 0.061 103. 0.533 k (hr-1) 6. 13 32. 38.1 56. 14 80. 11.3 104. 13 T 1/2 (hr) 7. 891 33. 1044 57. 303 81. 595 105. 356 AUC (mg/L*hr) 8. 99 34. 97 58. 99.97 82. 99 106. 99 % Cl h 9. 1 35. 3 59. 0.03 83. 1 107. 1 % Cl r 10. 0.533 36. 0.182 60. 1.57 84. 0.798 108. 0.533 Cl tot (L/hr) 11. 0.528 37. 0.177 61. 1.57 85. 0.790 109. 0.528 Cl h (L/hr) 12. 0.005 38. 0.005 62. 0.005 86. 0.008 110. 0.005 Cl r (L/hr) 13. 0.005 Eh 14. 0.000067 Er 15. 26.5 39. 8.84 63. 26.5 87. 26.5 111. 13.26 (L/hr) Cl h int 16. 0.267 40. 0.267 64. 0.00889 88. 0.267 112. 0.133 (L/hr) Cl r int 17. 1 41. 1 65. 1 89. 1 113. 1 FR h 18. 1 42. 0.333 66. 3 90. 1.5 114. 1 FI h 19. 1 43. 1 67. 1 91. 1 115. 1 FR r 20. 1 44. 1 68. 0.1 92. 1.5 116. 1 FI r 21. 1 45. 0.341 69. 2.94 93. 1.5 117. 1 FCL τ (hr) 22. 12 46. 12 70. 12 94. 12 118. 8 15-36 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 23. 0.923 47. 0.315 71. 0.857 95. 1.06 119. 0.615 N 24. 2.01 48. 1.94 72. 2.01 96. 2.1 120. 2.2 µg ss  ------- Cp -  mL max free 25. 1.5 49. 1.74 73. 1.5 97. 1.5 121. 1.78 µg ss  ------- Cp -  mL avg free 26. 1.06 50. 1.55 74. 1.1 98. 1.01 122. 1.42 µg ss  ------- Cp -  mL min free 15-37 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 15.8.3 1. Dose = 500 mg (given) 2. Bioavailability (f) = 0.95 (given) 3. Unbound Fraction = 0.02 (given) 4. V d = 10L (given) 0.693 –1 5. k = ------------ = 0.0533hr - t1 ⁄ 2 6. t 1 ⁄ 2 = 13hr (given) f ⋅ Dose 7. AUC = ------------------- = 891L k ⋅ Vd 8. %Cl h = 100 – %Cl r = 99 9. %Cl r = 1 (given) 10. Cl tot = k ⋅ V d = 0.533L ⁄ hr 11. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr 12. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr Cl h 13. E h = ------- = 0.00528 - Qh Cl r 14. E r = ------- = 0.000067 - Qr Q ⋅ Cl h ------------------ Q – Cl h = ------------------ = 26.5L ⁄ hr 15. Cl h - fu int Q ⋅ Cl r ----------------- - Q – Cl r = ----------------- = 0.267L ⁄ hr 16. Cl r - fu int 17. FR h = 1 (given) 18. FI h = 1 (given) 15-38 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 19. FR r = 1 (given) 20. FI r = 1 (given) 21. F Cl = 1 (given) 22. τ = 12hr (given) τ 23. N = -------- = 0.923 - t1 ⁄ 2 fu ⋅ S ⋅ f ⋅ D µg ss 1 = -------------------------- ⋅ -------------------- = 2.0 ------- Cp - 24. N  1 V mL max free 1 –  -- - 2 f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg ss Cp = -------------------------- = ----------------------------- = 1.5 ------- - - 25. V⋅K⋅τ V ⋅ 0.693 ⋅ N mL avg free N  1 -- -  2 fu ⋅ S ⋅ f ⋅ D µg ss = -------------------------- ⋅ -------------------- = 1.1 ------- Cp - 26. N 1 –  -- 1 V mL min free - 2 27. Dose = mg 28. Bioavailability (f) = 0.95 (no change) 29. Unbound Fraction = 0.02 (no change - given) 30. V d = 10L (given) 0.693 –1 31. k = ------------ = 0.0533hr - t1 ⁄ 2 32. t 1 ⁄ 2 = 13hr (given) f ⋅ Dose 33. AUC = ------------------- = 891L k ⋅ Vd 34. %Cl h = 100 – %Cl r = 99 35. %Cl r = 1 (given) 36. Cl tot = k ⋅ V d = 0.533L ⁄ hr 37. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr 15-39 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 38. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr Q ⋅ Cl h ------------------ Q – Cl h = ------------------ = 26.5L ⁄ hr 39. Cl h - fu int Q ⋅ Cl r ----------------- - Q – Cl r = ----------------- = 0.267L ⁄ hr 40. Cl r - fu int 41. FR h = 1 (given) 42. FI h = 1 (given) 43. FR r = 1 (given) 44. FI r = 1 (given) 45. F Cl = 1 (given) 46. τ = 12hr (given) τ 47. N = -------- = 0.923 - t1 ⁄ 2 fu ⋅ S ⋅ f ⋅ D µg ss 1 = -------------------------- ⋅ -------------------- = 2.0 ------- Cp - 48. N  1 V mL max free 1 –  -- - 2 f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg ss Cp = -------------------------- = ----------------------------- = 1.5 ------- - - 49. V⋅K⋅τ V ⋅ 0.693 ⋅ N mL avg free N  1  -- - fu ⋅ S ⋅ f ⋅ D µg ss 2 = -------------------------- ⋅ -------------------- = 1.1 ------- Cp - 50. N  1 V mL min free 1 –  -- - 2 51. Dose = mg 52. Bioavailability (f) = 0.95 (no change) 53. Unbound Fraction = 0.02 (no change - given) 54. V d = 10L (given) 15-40 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 0.693 –1 55. k = ------------ = 0.0533hr - t1 ⁄ 2 56. t 1 ⁄ 2 = 13hr (given) f ⋅ Dose 57. AUC = ------------------- = 891L k ⋅ Vd 58. %Cl h = 100 – %Cl r = 99 59. %Cl r = 1 (given) 60. Cl tot = k ⋅ V d = 0.533L ⁄ hr 61. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr 62. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr Q ⋅ Cl h ------------------ Q – Cl h = ------------------ = 26.5L ⁄ hr 63. Cl h - fu int Q ⋅ Cl r ----------------- - Q – Cl r = ----------------- = 0.267L ⁄ hr 64. Cl r - fu int 65. FR h = 1 (given) 66. FI h = 1 (given) 67. FR r = 1 (given) 68. FI r = 1 (given) 69. F Cl = 1 (given) 70. τ = 12hr (given) τ 71. N = -------- = 0.923 - t1 ⁄ 2 fu ⋅ S ⋅ f ⋅ D µg ss 1 = -------------------------- ⋅ -------------------- = 2.0 ------- Cp - 72.  1 N V mL max free 1 –  -- - 2 15-41 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg ss Cp = -------------------------- = ----------------------------- = 1.5 ------- - - 73. V⋅K⋅τ V ⋅ 0.693 ⋅ N mL avg free  1 N  -- - fu ⋅ S ⋅ f ⋅ D µg ss 2 = -------------------------- ⋅ -------------------- = 1.1 ------- Cp - 74. 1 –  -- 1 N V mL min free - 2 75. Dose = mg 76. Bioavailability (f) = 0.95 (no change) 77. Unbound Fraction = 0.02 (no change - given) 78. V d = 10L (given) 0.693 –1 79. k = ------------ = 0.0533hr - t1 ⁄ 2 80. t 1 ⁄ 2 = 13hr (given) f ⋅ Dose 81. AUC = ------------------- = 891L k ⋅ Vd 82. %Cl h = 100 – %Cl r = 99 83. %Cl r = 1 (given) 84. Cl tot = k ⋅ V d = 0.533L ⁄ hr 85. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr 86. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr Q ⋅ Cl h ------------------ Q – Cl h = ------------------ = 26.5L ⁄ hr 87. Cl h - fu int Q ⋅ Cl r ----------------- - Q – Cl r = ----------------- = 0.267L ⁄ hr 88. Cl r - fu int 89. FR h = 1 (given) 90. FI h = 1 (given) 15-42 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 91. FR r = 1 (given) 92. FI r = 1 (given) 93. F Cl = 1 (given) 94. τ = 12hr (given) τ 95. N = -------- = 0.923 - t1 ⁄ 2 fu ⋅ S ⋅ f ⋅ D µg ss 1 = -------------------------- ⋅ -------------------- = 2.0 ------- Cp - 96. N  1 V mL max free 1 –  -- - 2 f u ⋅ S ⋅ f ⋅ D fu ⋅ S ⋅ f ⋅ D µg ss Cp = -------------------------- = ----------------------------- = 1.5 ------- - - 97. V⋅K⋅τ V ⋅ 0.693 ⋅ N mL avg free N  1 -- -  2 fu ⋅ S ⋅ f ⋅ D µg ss = -------------------------- ⋅ -------------------- = 1.1 ------- 98. Cp - N 1 –  -- 1 V mL min free - 2 99. Dose = mg 100. Bioavailability (f) = 0.95 (no change) 101. Unbound Fraction = 0.02 (no change - given) 102. V d = 10L (given) 0.693 –1 103. k = ------------ = 0.0533hr - t1 ⁄ 2 104. t1 ⁄ 2 = 13hr (given) f ⋅ Dose 105. AUC = ------------------- = 891L k ⋅ Vd 106. %Cl h = 100 – %Cl r = 99 107. %Cl r = 1 (given) 108. Cl tot = k ⋅ V d = 0.533L ⁄ hr 109. Cl h = Cl tot ⋅ %Cl h = 0.528L ⁄ hr 15-43 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/
    • Practice Exams: Exam 2 110. Cl r = Cl tot ⋅ %Cl r = 0.005L ⁄ hr Q ⋅ Cl h ------------------ Q – Cl h = ------------------ = 26.5L ⁄ hr 111. Cl h - fu int Q ⋅ Cl r ----------------- - Q – Cl r = ----------------- = 0.267L ⁄ hr 112. Cl r - fu int 113. FR h = 1 (given) 114. FI h = 1 (given) 115. FR r = 1 (given) 116. FI r = 1 (given) 117. F Cl = 1 (given) 118. τ = 12hr (given) τ 119. N = -------- = 0.923 - t1 ⁄ 2 fu ⋅ S ⋅ f ⋅ D µg ss 1 = -------------------------- ⋅ -------------------- = 2.0 ------- Cp - 120. N  1 V mL max free 1 –  -- - 2 fu ⋅ S ⋅ f ⋅ D f u ⋅ S ⋅ f ⋅ D µg ss Cp = -------------------------- = ----------------------------- = 1.5 ------- - - 121. V⋅K⋅τ V ⋅ 0.693 ⋅ N mL avg free N  1  -- - fu ⋅ S ⋅ f ⋅ D µg ss 2 = -------------------------- ⋅ -------------------- = 1.1 ------- 122. Cp - N  1 V mL min free 1 –  -- - 2 15-44 Basic Pharmacokinetics REV. 99.4.25 Copyright © 1996-1999 Michael C. Makoid All Rights Reserved http://kiwi.creighton.edu/pkinbook/