Enzyme Induction by Rifampicin and Its Time-Dependent Pharmacokinetics

Pharmacokinetics and enzyme induction effects of rifampicin, an antituberculosis, were studied on 8 female and 2 male patients. Rifampicin (450 mg) was administered orally every morning before breakfast over a period of 8 weeks. On the 1st, 14th, 21st, 28th and 56th days of treatment, venous blood samples were drawn immediately, 2, 4 and 8 h after the administration of rifampicin. Rifampicin level in the serum was determined by high-performance liquid chromatography. Determination of rifampicin level was made in duplicate. Data of rifampicin levels in the serum (Ct) were calculated with a personal computer. Biexponential equation, Ct=A (e-Kat-e-Ket), and the pharmacokinetic parameters were non linear least squares regression analysis. The first-pass effect was obtained from calculated by the method of Gibaldi et al. Cmax and area under blood concentration curve gradually decreased until the 21st day of treatment and, thereafter, reached a steady-state until the 56th day of treatment. Biological half-life fluctuated until the 28th day of treatment and reached steady-state on day 28. Vd, Cl and first-pass effects showed a definite increase until the 21st day of treatment. After that, they reached a steady-state until the 56th day of treatment. In summary, pharmacokinetics of rifampicin was found to be time-dependent and closely related to the enzyme inducibility of the drug.