Mechanisms of inhibition of tolbutamide metabolism: Phenylbutazone, oxyphenbutazone, sulfaphenazole

Publisher Website
Google Scholar
Abstract
Tolbutamide half-life was increased by chronic administration of sulfaphenazole (9.5 hr to 28.6 hr, n =2), phenylbutazone (7.9 hr to 23.1 hr, n = 8), and oxyphenbutazone (8.1 hr to 30.2 hr, n = 2). The rate of elimination of tolbutamide was decreased within I to 2 hr of a single dose of sulJaphenazole and the tolbutamide half-life was increased from 9.2 hr to 25.7 hr (n = 2). In contrast, phenylbutazone and oxyphenbutazone, administered as single oral doses of 800 mg, had no immediate effect on tolbutamide elimination. At times greater than 20 to 30 hr after the single dose of phenylbutazone or oxyphenbutazone the rate of tolbutamide elimination was decreased. It is suggested that phenylbutazone and oxyphenbutazone act by inducing a form of cytochrome P-450 with low activity for tolbutamide hydroxylation. whereas sulJaphenazole acts by direct inhibition of the microsomal mixed function oxidase system.

This publication has 2 references indexed in Scilit: