BACKGROUND

We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats.

METHODS

Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl intra-peritoneal injection on day zero. Group, I rats did receive only CCl (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl and ATT administration, and rats were sacrificed on the last experiment day.

RESULTS

ATT treatment maintained the liver function changes initiated by CCl administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations.

CONCLUSION

The enzyme inhibitory capacity of isoniazid is well-preservd in CCl-induced liver injury.