103. non linear pharmacokinetics can be expected due to p) enzyme induction q) active secretion

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  1. both p and q are true
  2. p is true q is false
  3. q is true p is false
  4. both p and q are false


Saraswathi.B's picture


both p and q are true

Non linear pharmacokinetics is also called as mixed order or capacity limited kinetic. The rate process of the drugs ADME are dependent upon carrier or enzyme that are substrate specific have definite capacities and susceptibleto saturation at high drug concentration. in such cases an essentially first order rate process and the pharmacokinetics parameters change with the size of the admistered dose. the pharamcokinetics of such drugs are said to be dose dependent. drugs exhibiting such a kinetic profile are sources of variability in pharmacological response. several test to detect non linearity in the pharmacokinetcis

  • determination of steady state plasma concentration at different doses
  • determination of some of the important pharmacokinetics parameters.

causes of non linearity

drug absorption

  • it can be arises from 3 important sources
  • when the absorption is solubility rate limitied. eg: griseoflavin
  • when the absorption involves carrier mediated transport systems eg: absorption of riboflavin, ascorbic acid, cynacobalamin etc.
  • when the pre systemic gut wall or hepatic metabolism attains saturation. eg: propranolol, hydralazine, verapamil.

the parameters affected will be F, Ka, Cmax and AUC. a decrease in these parameters is observed in the former two cases and an increase in the latter case. other causes of non linearity in the drug absorption are changes in gastric emptying and GI blood flow and other physiological factors. non linearity in the drug absorption is of little consequence unless availability is drastically affected.

drug distribution

  • saturation of binding sites on the plasma proteins eg: phenyl butazone and naproxen.
  • saturation of tissue binding sites. eg: thiopental and fentanyl.

in both cases the free plasma drug concentration increases but Vd increases only in the former case whereas it decreases in the latter. clearance is also altered depending upon the extraction ratio of the drug. clearance of a drug with the high ER is greatly increased due to saturation of binding sites. unbound clearance of the drugs with the low ER is unaffected and one can expect an increases in pharmacological response.

drug metabolism

the non linear kinetics of most clinical importance is capacity limited metabolism at steady state dose administered of small changes can produce large variations in plasma concentration. it is a major source of large inter subject variability in pharmacological response.

two important causes of non linearity

  • capacity limited metabolism due to enzyme and or co factor saturation. eg: phenytoin, alcohol, theophylline etc.
  • enzyme induction. eg: carbamazepine

saturation of the enzyme results in decreased ClH and therefore increased Css. reserve is true for enzyme induction. other causes of non linearity in bio transformation include saturation of binding sites, inhibitory effect of the metabolite on enzyme and pathological situations such as hepatotoxicity and changes in hepatic blood flow.

drug excretion

the two active processes in renal excretion

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