The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats

✍ Scribed by Helen M. Baldan; Helene J. De Rosa; Iguatemy L. Brunetti; Valdecir F. Ximenes; Rosângela G. P. Machado

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 99 KB
• Volume: 28
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.570

✦ Synopsis

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 þ RMP 100 mg; INH 100 mg þ PYR 350 mg; INH 100 mg þ PYR 350 mg þ 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 1/2b

) 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 þ PYR þ 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.