Summary
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 in the area under plasma concentration-time curves indicating oral absorption was complete and no apparent first-pass metabolism occurred. 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 ± 0.4121) than after oral (5.936 ± 1.607 1) 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.
Similar content being viewed by others
References
Richard M.L., Prince R.A., Kenaley, K.A. (1981): Antimicrobial penetration into cerebrospinal fluid. Drug Intell. Clin. Pharm., 15, 341–365.
Martindale (1986): The Extra Pharmacopoeia 28th edn. London: The Pharmaceutical Press, pp 1564–1585.
Chan K., Wong C.L., Wai, M.K. (1986): Anti-tuberculous drug penetration into cerebrospinal fluid in a rabbit model, Asia Pacific J. Pharmacol., 1, 41–45.
Chan K., Wong C.L., Lok S. (1986): High performance liquid chromatographic determination of pyrazinamide in cerebrospinal fluid and plasma in the rabbit. J. Chromatogr. 380, 367–373.
Gibaldi M., Perrier D. (1982): Pharmacokinetics. In: Drugs and the Pharmaceutical Science. Vol. 15. 2nd Edn. New York, Marcel Dekker.
Tang L-M., Swash, M. (1985). Tuberculosis of the nervous system: a modern problem. J. Roy. Soc. Med. 78, 429–432.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chan, K., Wong, C.L. Pharmacokinetics of pyrazinamide in plasma and CSF of rabbits following intravenous and oral administration. European Journal of Drug Metabolism and Pharmacokinetics 13, 195–199 (1988). https://doi.org/10.1007/BF03189939
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03189939