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The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats.
Biopharm Drug Dispos. 2007 Nov; 28(8):409-13.BD

Abstract

Tuberculosis chemotherapy involves combination of the drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) for a 6-month period. The present work investigated the influence of RMP and PYR on the pharmacokinetic parameters of INH when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg+RMP 100 mg; INH 100 mg+PYR 350 mg; INH 100 mg+PYR 350 mg+RMP 100 mg. It was found that the co-administration of PYR caused an increase in the INH distribution volume (V(d)/F), half-life of elimination (t(1/2beta)) and clearance (Cl(T)/F), and a decrease in the area under curve 0 to 24 h (AUC). Co-administration of RMP caused an increase in the Cl(T)/F and a decrease in the AUC. The combination INH+PYR+RMP caused an increase in the Cl(T)/F and a decrease in the AUC. These significant pharmacokinetic interactions between the tuberculostatic drugs might be related to differences in the therapeutic and toxic effects.

Authors+Show Affiliations

Departamento de Princípios Ativos Naturais e Toxicologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP, Brasil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17828712

Citation

Baldan, Helen M., et al. "The Effect of Rifampicin and Pyrazinamide On Isoniazid Pharmacokinetics in Rats." Biopharmaceutics & Drug Disposition, vol. 28, no. 8, 2007, pp. 409-13.
Baldan HM, De Rosa HJ, Brunetti IL, et al. The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats. Biopharm Drug Dispos. 2007;28(8):409-13.
Baldan, H. M., De Rosa, H. J., Brunetti, I. L., Ximenes, V. F., & Machado, R. G. (2007). The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats. Biopharmaceutics & Drug Disposition, 28(8), 409-13.
Baldan HM, et al. The Effect of Rifampicin and Pyrazinamide On Isoniazid Pharmacokinetics in Rats. Biopharm Drug Dispos. 2007;28(8):409-13. PubMed PMID: 17828712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats. AU - Baldan,Helen M, AU - De Rosa,Helene J, AU - Brunetti,Iguatemy L, AU - Ximenes,Valdecir F, AU - Machado,Rosângela G P, PY - 2007/9/11/pubmed PY - 2008/1/24/medline PY - 2007/9/11/entrez SP - 409 EP - 13 JF - Biopharmaceutics & drug disposition JO - Biopharm Drug Dispos VL - 28 IS - 8 N2 - Tuberculosis chemotherapy involves combination of the drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) for a 6-month period. The present work investigated the influence of RMP and PYR on the pharmacokinetic parameters of INH when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg+RMP 100 mg; INH 100 mg+PYR 350 mg; INH 100 mg+PYR 350 mg+RMP 100 mg. It was found that the co-administration of PYR caused an increase in the INH distribution volume (V(d)/F), half-life of elimination (t(1/2beta)) and clearance (Cl(T)/F), and a decrease in the area under curve 0 to 24 h (AUC). Co-administration of RMP caused an increase in the Cl(T)/F and a decrease in the AUC. The combination INH+PYR+RMP caused an increase in the Cl(T)/F and a decrease in the AUC. These significant pharmacokinetic interactions between the tuberculostatic drugs might be related to differences in the therapeutic and toxic effects. SN - 0142-2782 UR - https://www.unboundmedicine.com/medline/citation/17828712/The_effect_of_rifampicin_and_pyrazinamide_on_isoniazid_pharmacokinetics_in_rats_ L2 - https://doi.org/10.1002/bdd.570 DB - PRIME DP - Unbound Medicine ER -