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
Dcsacetylrifampicin 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 basis
of 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 in respect of
Isoniazid in slow acetylators to lessen the risk of
toxic reactions
