THE PHARMACOKINETICS OF ISONIAZID AND HYDRAZINE METABOLITE IN PLASMA AND CEREBROSPINAL-FLUID OF RABBITS

The pharmacokinetics of isoniazid (INH) and hydrazine metabolite (HYD) in plasma and cerebrospinal fluid (CSF) of ten rabbits was studied after separate intravenous (i.v.) and oral (p.o.) administration in a crossover study. The concentrations of INH and HYD in the biological fluids were determined by high performance liquid chromatography (HPLC). There was no difference in the area under plasma concentration-time curves, indicating that oral absorption was complete. The mean apparent volume of distribution after i.v. (3.02 +/- 0.55 L) was smaller (p < 0.01) than that after p.o. (4.29 +/- 1.25 L) dosing. The elimination t 1/2 of INH in CSF was longer (p < 0.005) than that in plasma after either route of administration. There was no significant barrier to the penetration of INH into the CSF from the general circulation. The HYD plasma concentrations were similar after either route. HYD was eliminated at a slower rate (Ke = 0.17 h-1) than INH (Ke = 0.59 h-1). There was prolonged exposure of the body to HYD (> 6 h - above 0.1-mu-g/ml).