The disposition of antituberculous drugs in plasma of elderly patients. I. Isoniazid and hydrazine metabolite.

The plasma profiles of isoniazid (INH) and hydrazine (HYD) metabolite were compared in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month after treatment for tuberculosis with INH, rifampicin (RIF) and pyrazinamide (PZA). There was no difference in the pharmacokinetics of INH between the two age groups. The clearance for INH at steady-state was significantly lower than after the first dose. After the first dose the maximum concentration (Cmax) for HYD was significantly higher (p less than 0.05) in the elderly (0.4 +/- 0.07 microgram/ml) than in the young (0.24 +/- 0.08 microgram/ml). HYD is produced in significant amounts during INH metabolism and this should not be neglected when evaluating INH related toxicity.