Decreased acetylation of isoniazid in chronic renal failure

Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were compared with parameters obtained from 14 patients with chronic renal failure. In the 29 normal rapid acetylators and eight normal slow acetylators, the mean plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours, respectively. The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepatic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of isoniazid were reevaluated in the same patients with chronic renal failure after the kidney transplantation. After successful kidney transplantation, the shortening of isoniazid half-life was pronounced and the nonrenal clearance was markedly increased. These findings indicate that decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.