The pharmacokinetics of pyrazinamide (PZA) in cerebrospinal fluid (CSF) and plasma of 10 rabbits were studied after separate intravenous (i.v.) and oral (p.o.) administration, in a cross-over study. Concentrations of PZA in biological fluids were determined by high-performance liquid chromatography (HPLC). After p.o. dose PZA was absorbed rapidly and peak plasma concentration was attained at 0.5 h post administration. After i.v. dose, the plasma PZA concentrations declined rapidly within 10 min and subsequently more slowly following a bi-exponential manner. No difference was observed int he area under plasma concentration-time curves indicating oral absorption was complete and no apparent first-pass metabolism occured. The (mean ± S.D.) elimination t1/2 after i.v. (1.04 ± 0.18 h) was significantly shorter (p = 0.0005) than that after oral (1.95 ± 0.63 h) dose and the apparent volume of distribution was also significantly smaller (P = 0.005) after i.v. (3.211 ± 0.412 l) than after oral (5.936 ± 1.607 l) administration. The elimination t1/2 of PZA in CSF was nearly identical to that in plasma after either i.v. (1.07 ± 0.20 h) or p.o. (1.84 ± 0.56 h) administration. There is no apparent barrier in rabbits for the penetration of PZA into CSF from the general circulation.
Available at: http://works.bepress.com/kelvin_chan/110/