A STUDY OF RENAL CLEARANCES, METABOLIC INACTIVATION RATES, AND SERUM FALL-OFF INTERACTION OF ISONIAZID AND PARA-AMINOSALICYLIC ACID IN MAN

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Abstract
Studies to determine the relative contribution of the renal clearance and metabolic inactivation rate to the intravenous half-life of isoniazid and para-aminosalicylic acid (PAS) in humans are described. Both rapid and slow isoniazid-inactivation categories are compared. The apparent distribution volumes and serum protein-binding for both drugs have been determined as part of these studies. Serum protein-binding of isoniazid as determined by ultrafiltration is quantitatively negligible in the two groups. The renal clearance of isoniazid contributes only a small part to the serum decay rates in both rapid and slow inactivators. By contrast, renal and metabolic factors appear to be of about equal importance for PAS, and show no significant differences in the two isoniazid-inactivation categories. Four grams of PAS by mouth caused a significant mean prolongation of the intravenous half-life of isoniazid in 21 patients tested. If isoniazid acetylation in the two inactivation groups is mediated simply by differences in quantity of an identical acetylase, then, with certain reservations, isoniazid and PAS do not appear to be acetylated exclusively by the same enzyme. Several alternatives are proposed.