NON LINEAR PHARMAKOKINETICS BPPK 6thSEM

1. NONLINEAR
PHARMACOKINETICS
-:PRESENTED BY:-
BANDARI PRANAY
BIOPHARMACEUTICS AND PHARMACOKINETICS,
BHARAT INSTITUTE OF TECHNOLOGY.

2. LINEAR PHARMACOKINETICS
 Change in plasma concentration due to ADME process is proportional
to dose of drug administered (single or multiple doses)
 Follow First order kinetics[linear kinetics]
 Semi-log plot for concentration vs time is super imposable (Principle of
superimposition)
 No change in F, Ka, Ke, Vd, Clearance etc.
 Pharmacokinetics is dose independent

3. NONLINEAR PHARMACOKINETICS
 Rate process of ADME are dependent on carrier or enzymes having
definite capacity and subjected to saturation.
 Change in concentration is no more proportional to dose administered
during the total process of ADME.
 Follow First order + Zero order kinetics
 Change in different pharmacokinetic parameters
 It is also called as mixed-order ,nonlinear and capacity limited kinetics

4. DETECTION OF NONLINEARITY IN
PHARMACOKINETICS
There are several tests to detect nonlinearity in pharmacokinetics, they are:
1. Determination of steady state plasma conc at different doses.
2. Determination of some of the important pharmacokinetics
parameters such as
a) Fraction variable
b) Bioavailable
c) Elimination half life
d) Total systemic clearance

5. CAUSES OF NONLINEARITY
 Nonlinearities can occur in drug ADME
1. DRUG ABSORBTION
a. Absorption is solubility or dissolution rate limited eg. Griseofulvin.
b. Absorption involve carrier mediated transportation eg. Riboflavin,
ascorbic acid.
c. Hepatic metabolism attain saturation eg. Propranolol, hydralazine.
2. DRUG DISTRIBUTION
a. Saturation of binding sites on plasma proteins eg. Phenylbutazone,
naproxen.
b. Saturation of tissue binding sites eg. Thiopental, fentanyl.

6. 3. DURING METABOLISM
a. Capacity limited metabolism due to enzyme or cofactor saturation
eg. Alcohol, Phenytoin.
b. Enzyme induction eg. Carbamazepin.
4. DURING EXCRETION
a. Active tubular secretion eg. Penicillin G.
b. Active tubular re-absorption eg. Glucose, water soluble vitamins.
c. Other sources: Forced Diuresis, change in urine pH, nephrotoxicity
etc.
CAUSES OF NONLINEARITY

7. MICHAELIS MENTEN EQUATION
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8. MICHAELIS MENTEN EQUATION
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14. REFERNECES:
 Biopharmaceutics and Pharmacokinetics a treatise by D.M.
BRAHMANKAR and SUNIL B.JAISWAL,
 Internet.

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