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Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
Pharmacokinetics: Lecture two
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Pharmacokinetics: Lecture two

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IV Bolus One Compartment First Order Model

IV Bolus One Compartment First Order Model

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  • 1. Intravenous Bolus Administration Anas Bahnassi PhD RPhOne compartment Model
  • 2. LECTURE’S OBJECTIVESUpon the completion of this lecture the student should be able to:• Describe the different pharmacokinetic parameters.• Determine pharmacokinetic parameters from either plasma or urinary data.• State the equation for plasma drug concentration as a function of time.• Calculate the corresponding plasma drug concentration at time t• Calculate the intravenous bolus dose of a drug that will result in a target (desired) plasma drug concentration at time t. Anas Bahnassi PhD 2011 2
  • 3. XAssumptions • One-compartment model. Xu • First-order process. • Passive diffusion. • No metabolism takes place (elimination is 100% via renal excretion) • The drug is being monitored in blood (plasma/serum) and urine. 3 Anas Bahnassi PhD 2011
  • 4. Anas Bahnassi PhD 2011 4
  • 5. IV Bolus Equations:Anas Bahnassi PhD 2011 5
  • 6. Pharmacokinetic Parameters• Apparent volume of distribution (Vd).• Elimination half-life (t1/2).• Elimination rate constant (K0 or Kel).• Systemic clearance (Cls). Anas Bahnassi PhD 2011 6
  • 7. Apparent volume of distribution (Vd)• Concentrations are usually measured not masses.• Vd is a proportionality constant whose sole purpose is to relate the plasma concentration (Cp) and the mass of drug (X) in the body at a time.• It is not a physical volume. Anas Bahnassi PhD 2011 7
  • 8. Vd ConceptDrug Concentration in Beaker Drug Concentration in Beaker with charcoal Dose = 10mg Dose = 10mg Cp0 = 20mg/L Cp0 = 2mg/L Vd= 500mL Vd= 5000mL The concentration of KI is different although the volume of water in both beakers is the same. Anas Bahnassi PhD 2011 8
  • 9. Calculating Vd Apparent volumes = of distribution are given in units of volume (e.g. mL) or units of volume on a body weight basis (Lkg-1 body weight).Anas Bahnassi PhD 2011 9
  • 10. Elimination Half life (t1/2) The time (h, min, day, etc.) at which the mass (or Semi-logarithmic Paper amount) of unchanged drug becomes half (or 50%) of the initial mass of drug. Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009 10Anas Bahnassi PhD 2011
  • 11. Elimination Half life (t1/2)When Cp = 0.5 (Cp)0 t = t1/2 Anas Bahnassi PhD 2011 11
  • 12. Elimination Rate Constant (k)Unit of k in first order process is reciprocal of time (h-1) = + Elimination Rate Constant Metabolism Rate Excretion Constant Rate Constant Anas Bahnassi PhD 2011 12
  • 13. Elimination Rate Constant (k) X0= 0.963 = = 0.173ℎ −1 250mg 4 125 % = 100 = 50% 250 M1= 75 75mg% = 100 = 30% 250 50% = 100 = 20% 250 M2= 50mg = %. = . − = %. = . − = %. = . − Xu= 125mg Anas Bahnassi PhD 2011 13
  • 14. Drawing a best-fit line through the Data Anas Bahnassi PhD 2011 14
  • 15. 40 X = 61.827e-0.526t353025201510 RL paper5 150 0 1 2 3 4 5 6 7 8 9 10 Anas Bahnassi PhD 2011
  • 16. Calculating PK Parameters From the SL graph 0 t½= 1.3h = 0 Cp0= 63mg/mL. 600000 = = 9523.8 63 = 9.5238 . = . Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009 16 Anas Bahnassi PhD 2011
  • 17. Use of Urinary DataAmount remained to be excreted Rate of Excretion1. Urine collection is a non-invasive technique.2. More convenient sample collection3. Sample size is not restricting.4. The sampling time reflects cumulative drug concentration in urine collected over a period of time, rather than a drug concentration at a discrete time.5. Urinary data allows direct measurement of bioavailability, both absolute and relative, without the need of fitting the data to a mathematical model. 17 Anas Bahnassi PhD 2011
  • 18. Use of Urinary Data X Cumulative amount Xu = In Urine at time (t) = 0 (1 − − ) Administered dose of drug Excretion Rate = ∞ Constant = 0 Anas Bahnassi PhD 2011 18
  • 19. Amount Remaining To be excreted ∞ − = = ℎ = Drug Totally Drug Totally Removed Unchanged Removed Unchanged Can not calculate Volume of Distribution 19 Anas Bahnassi PhD 2011
  • 20. Limitations1. Keep obtaining urine samples until noadditional drug practically appears in the urine,(t = 7 t½)2. Urine samples can not be lost, or urine fromany samples used in the determination of Xu(the exact volume of urine at each time intervalmust be known)3. A time-consuming method for a drug with along elimination half life.4. There is a cumulative build up of error. Anas Bahnassi PhD 2011 20
  • 21. Dose = 80mg The plot represents the cumulative quantity Anas Bahnassi PhD 2011 of the medication from the collected urine Drug TotallyRemoved Unchanged samples vs. the time. 21 Basic Pharmacokinetics: S. Jambhekar , Phillip Breen 2009
  • 22. The plot represents the amount remaining to be excreted of the medication vs. time Drug Totally Removed Unchanged = Can not calculate Anas Bahnassi PhD 2011 Volume of Distribution 22
  • 23. Rate of Excretion Method = = − = − average time between urine collectionaverage rateof excretion Anas Bahnassi PhD 2011 23
  • 24. The plot represents average rate ofexcretion within the time interval between samples collection vs. average time between urine samples collection Anas Bahnassi PhD 2011 24
  • 25. 25Anas Bahnassi PhD 2011
  • 26. 0.693 0.693 = = = = 0.693ℎ −1 Anas Bahnassi PhD 2011 ½ 1 26
  • 27. Questions:What is the concentration of drug 0, 2 and 4 hours after a dose of 500mg. Known pharmacokinetic parameters are apparent volume ofdistribution, Vd is 30 liter and the elimination rate constant, kel is 0.2hr-1 ?From the plot seen calculate allpharmacokinetic parameters thatyou can calculate Anas Bahnassi PhD 2011 27
  • 28. PharmacokineticsAnas Bahnassi PhD RPh abahnassi@gmail.com http://www.linkedin.com/in/abahnassi http://www.slideshare.net/abahnassi http://bahnassi.coursesites.com attribution – non-commercial – share alike

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