Single-dose pharmacokinetics of isoniazid and rifampicin in patients with chronic renal failure.
Prema Gurumurthy; Raghupati Sarma, G.; Jayasankar, K.; Thyagarajan, K.; Prabhakar, R.; Muthusethupathi, M.A.; Sampathkumar, P.; Shivakumar, S.
Indian Journal of Tuberculosis; 1992; 39; 221-228.
The pharmacokinetics of Isoniazid and Rifampicin were studied in 18 patients with mild or moderate renal failure (creatinine clearance : 10.1-50.0 ml/min) and 17 patients with severe renal failure (creatinine clearance < 10.0 ml/min) and the findings compared with those in 16 healthy subjects. The renal excretion of Isoniazid, Acetylisoniazid, Rifampicin and Desacetylrifampicin was severely inhibited in patients with renal failure. Plasma Rifampicin and Isoniazid concentrations in rapid acetylators were similar in healthy subjects and both the groups of patients. In slow acetylators, plasma Isoniazid concentrations and exposure (AUC) and half-life of the drug, calculated on the basisof these concentrations were appreciably higher in patients than in healthy subjects (p < 0.01); the mean values in the two groups of patients were, however, similar. The correlations between plasma creatinine or creatinine clearance and peak concentration, exposure or half-life of Isoniazid were poor (r < 0.28) in the slow acetylators. These findings suggest that in patients with renal failure, it is not necessary to reduce dosage of Rifampicin or of Isoniazid in rapid acetylators but advisable irrespect of Isoniazid in slow acetylators to lessen the risk of toxic reactions.
Back to List of publications / Home |