Example: Isoniazid is a drug used in the treatment of tuberculosis. Its half-life in individuals with normal liver function is 1 hour, and in individuals with reduced liver function is 6 hours. If the change in liver function does not affect isoniazid Vd (50L), calculate the average CLT and AUC after administration of a single oral dose of 500 mg in both patient populations (F=1).

a- Individuals with normal liver function

CLT =

0.693

1 hr x 50L = 34.65 L/hr
AUC =

(1) 500mg

34.65 L/hr = 14.43 mg-hr/L
half life (hr)
Longer half life means slower rate of drug elimination which results from the lower CLT. The lower CLT results in proportional increase in the AUC.

b- Individuals with reduced liver function

CLT =

0.693

6 hr x 50L = 5.78 L/hr
AUC =

(1) 500mg

5.78 L/hr = 86.5 mg-hr/L
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