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Pharmacokinetic variability<br />
varibility<br />INTRERINDIVIDUAL VARIBILITY<br />             INTRAINDVIDUAL VARIBILITY<br />
INTRERINDIVIDUAL VARIBILITY<br />The dose required to produce action varies from indvidual to indvidual<br />The doses ref...
Varibility in doses<br />The variability in dose of warfarin required to produce  similar prothrombin action in 200 patien...
Interindividual variability<br />Change in plasma concentration of same subject when given in different occasion<br />Caus...
histogram<br />A.The plateau plasma con varies widely in260 patients receiving 25mg of nortryptiline orally three times da...
 steps to Indvidlisation <br />
Over view<br />
Describing variability<br />A,B  are unimodel  but  C is bimodal signifying  that they are are two major groups with in po...
Factors causing varibility<br />
The development and subsequent marketing of drug<br />
OBESITY<br />PHARMACOKINTIC VARIBILITY<br />
OBESITY<br />                    a condition that is characterized by excessive accumulation and storage of fat in the bod...
Drug administration<br />Drug administration in obese patients is difficult because recommended doses are based on pharmac...
Obesity affects<br />pharmacokinetic parameters-<br />volume of distribution (Vd),<br /> clearance (Cl)<br /> protein bind...
Body mass index<br />body mass index n a measure of body fat that is the ratio of the weight of the body in kilograms to t...
BMI<br />
Dosage regimen<br />
what ‘weight<br />clinician must appreciate what ‘weight’ should be used to calculate dosage: <br />totalbody weight (TBW)...
TBW  is actual body weight<br />IBW is estimated by<br /> x =100 for adult males<br />105 for adult females<br />
lbm<br />The percentage of fat and lean body mass<br />    calculated based on<br />  - height(cm)<br />   -Weight(kg)<br ...
Lean body mass<br />LBM can be calculated using the formulae<br />
dosage<br />Mostly, dosage recommendations in the package inserts are scaled to TBW<br />For obsity-<br />weight can then ...
                 NOMOGRAM(MALE)<br />Nomogram for male patients relating total body weight (kg), height<br />(cm), and gen...
               NOMOGRAM (FEMALES)<br />Nomogram for female patients relating total body weight (kg),<br />height (cm), and...
Lipophilic drugs<br />HIGHILY LIPOPHILICDRUGS<br />barbiturates and benzodiazepines   show significant increases in Vd  fo...
Volatile agents<br />Halothane is known to have considerable deposition in adipose tissue<br />hepatic metabolism- halotha...
Propofol<br />In morbidly obese patients, the induction dose of propofol can be calculated on IBW.<br />Although propofol ...
Drug metabolism<br />Neonates<br />
neonates<br />Invitro studies indicate that variability much greater in first three months of life declines to adult activ...
Enzymatic system  required for drug metabolism are higher in neonates and lower in adults <br />Chornic exposure of foetus...
differences<br />
Age groups<br />
                      PROTEIN BINDING<br />                                                                               ...
Protein binding<br />Plasma protein binding is less in newborn than adults <br /> Decrease Plasma protein binding is an in...
competatiion<br /> relative low plasma binding associated with elevated levels of biliubrin<br />Biluburin  binds with alb...
GENDER<br />
sex<br />Sex is an individual factor <br /> lead to interindividual differences in the metabolism of drugs<br />drugs that...
sex differences<br />muscle mass, <br />disposition of muscle tissue, <br />vascular resistance.<br /> gastric motility, <...
PHARMACOKINETIC CHANGES<br />volume of distribition and rate of metabolism changes <br />Volume of distrubution for centra...
Pharmacokinetic Properties<br />
references<br />Pharmacokinetics in obese patients                                                   by -Lu EC De Baerdema...
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Obsity

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M.PHARM PRACTICE
SRM CP CHENNAI

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Transcript of "Obsity"

  1. 1. Pharmacokinetic variability<br />
  2. 2. varibility<br />INTRERINDIVIDUAL VARIBILITY<br /> INTRAINDVIDUAL VARIBILITY<br />
  3. 3. INTRERINDIVIDUAL VARIBILITY<br />The dose required to produce action varies from indvidual to indvidual<br />The doses reflect the various dosage strength in market<br />
  4. 4. Varibility in doses<br />The variability in dose of warfarin required to produce similar prothrombin action in 200 patients varies widely<br />
  5. 5. Interindividual variability<br />Change in plasma concentration of same subject when given in different occasion<br />Causes-<br />Age ,sex,diseases, weight, drug interaction etc<br />High intrasubject variability difficult to prescribe the narrow therapeutic drugs<br />If high intrasubject variability in pharmacokinetic prescribed only if it has wide subject variability <br />
  6. 6. histogram<br />A.The plateau plasma con varies widely in260 patients receiving 25mg of nortryptiline orally three times daily<br />B.The con are log normally distrIbuted as seen in straight line<br />
  7. 7. steps to Indvidlisation <br />
  8. 8. Over view<br />
  9. 9. Describing variability<br />A,B are unimodel but C is bimodal signifying that they are are two major groups with in population With higher and lower clearance<br />
  10. 10. Factors causing varibility<br />
  11. 11. The development and subsequent marketing of drug<br />
  12. 12. OBESITY<br />PHARMACOKINTIC VARIBILITY<br />
  13. 13. OBESITY<br /> a condition that is characterized by excessive accumulation and storage of fat in the body and that in an adult is typically indicated by a body mass index of 30 or greater<br />
  14. 14. Drug administration<br />Drug administration in obese patients is difficult because recommended doses are based on pharmacokinetic data obtained from individuals with normal weights;<br />
  15. 15. Obesity affects<br />pharmacokinetic parameters-<br />volume of distribution (Vd),<br /> clearance (Cl)<br /> protein binding <br />changed for some drugs<br />i.v. anaesthetic drugs<br />inhalational anaesthetics<br />Lipophilic drugs<br />
  16. 16. Body mass index<br />body mass index n a measure of body fat that is the ratio of the weight of the body in kilograms to the square of its height in meters <br />
  17. 17. BMI<br />
  18. 18. Dosage regimen<br />
  19. 19. what ‘weight<br />clinician must appreciate what ‘weight’ should be used to calculate dosage: <br />totalbody weight (TBW),<br /> lean body mass (LBM)<br /> ideal body weight (IBW)?<br />
  20. 20. TBW is actual body weight<br />IBW is estimated by<br /> x =100 for adult males<br />105 for adult females<br />
  21. 21. lbm<br />The percentage of fat and lean body mass<br /> calculated based on<br /> - height(cm)<br /> -Weight(kg)<br /> -girth(inches)<br /> Percentage of fat = 90-2(height-girth)<br />
  22. 22. Lean body mass<br />LBM can be calculated using the formulae<br />
  23. 23. dosage<br />Mostly, dosage recommendations in the package inserts are scaled to TBW<br />For obsity-<br />weight can then be multiplied by the published doses scaled to TBW<br /> = WEIGHT×DOSE ON LABEL<br />
  24. 24. NOMOGRAM(MALE)<br />Nomogram for male patients relating total body weight (kg), height<br />(cm), and gender with lean body mass (LBM) using the formula<br />LBM = 1.1(weight) 128(weight/height)2.<br />
  25. 25. NOMOGRAM (FEMALES)<br />Nomogram for female patients relating total body weight (kg),<br />height (cm), and gender with lean body mass (LBM) using the formula<br />LBM = 1.07(weight) – 148(weight/height)2.<br />
  26. 26. Lipophilic drugs<br />HIGHILY LIPOPHILICDRUGS<br />barbiturates and benzodiazepines show significant increases in Vd for obese individuals. <br />.<br />Less lipophilic DRUGS<br />have little or no change in Vd with obesity<br />Exceptions to this is remifentanil,<br />
  27. 27. Volatile agents<br />Halothane is known to have considerable deposition in adipose tissue<br />hepatic metabolism- halothane hepatitis<br />
  28. 28. Propofol<br />In morbidly obese patients, the induction dose of propofol can be calculated on IBW.<br />Although propofol is highly lipophilic,does not accumulate in obese patients. <br />So the dosage of propofol for maintenance of anaesthesia in obese and lean same<br />
  29. 29.
  30. 30. Drug metabolism<br />Neonates<br />
  31. 31. neonates<br />Invitro studies indicate that variability much greater in first three months of life declines to adult activity<br />New born are higher for contreation toxicity due to development of delay drug metabolism<br />
  32. 32. Enzymatic system required for drug metabolism are higher in neonates and lower in adults <br />Chornic exposure of foetus to epliptic drugs leads to induction of drug metabolism enzymes <br />Sulfate conjugation seems to be efficient in newborn as in adults<br />Conjugation with glucornic acid reduced with increasing age<br />
  33. 33.
  34. 34.
  35. 35. differences<br />
  36. 36. Age groups<br />
  37. 37. PROTEIN BINDING<br /> NEONATES<br />
  38. 38. Protein binding<br />Plasma protein binding is less in newborn than adults <br /> Decrease Plasma protein binding is an increase in apparent volume of distribution in newborn<br />Low plasma binding is due to elevation of bilrubin<br />
  39. 39. competatiion<br /> relative low plasma binding associated with elevated levels of biliubrin<br />Biluburin binds with albumin and many compete with drugs binding <br />
  40. 40. GENDER<br />
  41. 41. sex<br />Sex is an individual factor <br /> lead to interindividual differences in the metabolism of drugs<br />drugs that are metabolized by hepatic oxidation have lower metabolic clearance and longer elimination half-lives in women who are on oral contraceptives<br />
  42. 42. sex differences<br />muscle mass, <br />disposition of muscle tissue, <br />vascular resistance.<br /> gastric motility, <br />secretion,<br /> metabolic rate<br />
  43. 43. PHARMACOKINETIC CHANGES<br />volume of distribition and rate of metabolism changes <br />Volume of distrubution for central compartment is more in males<br />Peripheral compartment of liophilic drug more in females<br />Ex- metablism of few drug in female oxazepam<br /> & metaprolol is slow in female<br />
  44. 44. Pharmacokinetic Properties<br />
  45. 45. references<br />Pharmacokinetics in obese patients by -Lu EC De Baerdemaeker MD<br /> slides of Approaching the In Silico Child<br /> Jeffrey S. Barrett, PhD, FCP<br /><ul><li>Biopharmaceutics and clinical pharmacokinetics</li></ul>milogibaldi ,PhD<br /><ul><li> Clinical Pharmacokinetics Concepts and Applications</li>
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