M.PHARM PRACTICE SRM CP CHENNAI

1. Pharmacokinetic variability

2. varibility INTRERINDIVIDUAL VARIBILITY INTRAINDVIDUAL VARIBILITY

3. INTRERINDIVIDUAL VARIBILITY The dose required to produce action varies from indvidual to indvidual The doses reflect the various dosage strength in market

4. Varibility in doses The variability in dose of warfarin required to produce similar prothrombin action in 200 patients varies widely

5. Interindividual variability Change in plasma concentration of same subject when given in different occasion Causes- Age ,sex,diseases, weight, drug interaction etc High intrasubject variability difficult to prescribe the narrow therapeutic drugs If high intrasubject variability in pharmacokinetic prescribed only if it has wide subject variability

6. histogram A.The plateau plasma con varies widely in260 patients receiving 25mg of nortryptiline orally three times daily B.The con are log normally distrIbuted as seen in straight line

7. steps to Indvidlisation

8. Over view

9. Describing variability A,B are unimodel but C is bimodal signifying that they are are two major groups with in population With higher and lower clearance

10. Factors causing varibility

11. The development and subsequent marketing of drug

12. OBESITY PHARMACOKINTIC VARIBILITY

13. OBESITY 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

14. Drug administration Drug administration in obese patients is difficult because recommended doses are based on pharmacokinetic data obtained from individuals with normal weights;

15. Obesity affects pharmacokinetic parameters- volume of distribution (Vd), clearance (Cl) protein binding changed for some drugs i.v. anaesthetic drugs inhalational anaesthetics Lipophilic drugs

16. Body mass index 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

17. BMI

18. Dosage regimen

19. what ‘weight clinician must appreciate what ‘weight’ should be used to calculate dosage: totalbody weight (TBW), lean body mass (LBM) ideal body weight (IBW)?

20. TBW is actual body weight IBW is estimated by x =100 for adult males 105 for adult females

21. lbm The percentage of fat and lean body mass calculated based on - height(cm) -Weight(kg) -girth(inches) Percentage of fat = 90-2(height-girth)

22. Lean body mass LBM can be calculated using the formulae

23. dosage Mostly, dosage recommendations in the package inserts are scaled to TBW For obsity- weight can then be multiplied by the published doses scaled to TBW = WEIGHT×DOSE ON LABEL

24. NOMOGRAM(MALE) Nomogram for male patients relating total body weight (kg), height (cm), and gender with lean body mass (LBM) using the formula LBM = 1.1(weight) 128(weight/height)2.

25. NOMOGRAM (FEMALES) Nomogram for female patients relating total body weight (kg), height (cm), and gender with lean body mass (LBM) using the formula LBM = 1.07(weight) – 148(weight/height)2.

26. Lipophilic drugs HIGHILY LIPOPHILICDRUGS barbiturates and benzodiazepines show significant increases in Vd for obese individuals. . Less lipophilic DRUGS have little or no change in Vd with obesity Exceptions to this is remifentanil,

27. Volatile agents Halothane is known to have considerable deposition in adipose tissue hepatic metabolism- halothane hepatitis

28. Propofol In morbidly obese patients, the induction dose of propofol can be calculated on IBW. Although propofol is highly lipophilic,does not accumulate in obese patients. So the dosage of propofol for maintenance of anaesthesia in obese and lean same

30. Drug metabolism Neonates

31. neonates Invitro studies indicate that variability much greater in first three months of life declines to adult activity New born are higher for contreation toxicity due to development of delay drug metabolism

32. Enzymatic system required for drug metabolism are higher in neonates and lower in adults Chornic exposure of foetus to epliptic drugs leads to induction of drug metabolism enzymes Sulfate conjugation seems to be efficient in newborn as in adults Conjugation with glucornic acid reduced with increasing age

35. differences

36. Age groups

37. PROTEIN BINDING NEONATES

38. Protein binding Plasma protein binding is less in newborn than adults Decrease Plasma protein binding is an increase in apparent volume of distribution in newborn Low plasma binding is due to elevation of bilrubin

39. competatiion relative low plasma binding associated with elevated levels of biliubrin Biluburin binds with albumin and many compete with drugs binding

40. GENDER

41. sex Sex is an individual factor lead to interindividual differences in the metabolism of drugs drugs that are metabolized by hepatic oxidation have lower metabolic clearance and longer elimination half-lives in women who are on oral contraceptives

42. sex differences muscle mass, disposition of muscle tissue, vascular resistance. gastric motility, secretion, metabolic rate

43. PHARMACOKINETIC CHANGES volume of distribition and rate of metabolism changes Volume of distrubution for central compartment is more in males Peripheral compartment of liophilic drug more in females Ex- metablism of few drug in female oxazepam & metaprolol is slow in female

44. Pharmacokinetic Properties