Hydrazine--a possible cause of isoniazid--induced hepatic necrosis

Pharmacokinetic parameters of isoniazid, hydrazine (a metabolite of isoniazid), rifampicin and pyrazinamide in a 74-year-old man with pulmonary tuberculosis who died of submassive hepatic necrosis eight days after starting antituberculosis therapy were compared with those of other elderly patients who did not develop hepatotoxicity. Steady-state plasma hydrazine and rifampicin concentrations in this patient exceeded twice the mean +/- 2 SD value for the group of patients without hepatotoxicity, while concentrations for isoniazid and pyrazinamide were comparable. The findings suggest that HYD may have a role in isoniazid-induced hepatic necrosis.