Pharmacokinetics of antituberculosis drugs in patients

The pharmacokinetics of rifampin, isoniazid, and ethambutol were determined in 26 ambulatory male patients (aged 49.5 +/- 9.9 yr) with tuberculosis. Rifampin and isoniazid were given individually or together, with or without ethambutol; studies were done after a single dose and after chronic administration. Under the study conditions, with large variability in the extent of disease and physical status and history of alcohol and tobacco abuse and narrow age range, the pharmacokinetics of these three antituberculosis drugs were not modified significantly by patient age. Furthermore, appreciable drug-drug interactions did not occur when the three drugs were administered concurrently. Self-induction of rifampin clearance by chronic dosing with the drug may lead to subtherapeutic levels of rifampin. Administration of isoniazid and ethambutol in two divided doses resulted in peak plasma concentrations below the accepted therapeutic levels of the two drugs. Our findings indicate that at least in the middle-aged patients with tuberculosis, the current single daily dose, multiple-drug regimen is therapeutically sound pharmacokinetically, and clinicians do not have to make adjustments in dosages of these drugs for age and the extent of disease.