Article date: May 1985
By: D.J. Back, J.F. Tjia in Volume 85, Issue 1, pages 121-126
Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo.
The 1‐substituted compounds 1‐methylimidazole, miconazole, clotrimazole and ketoconazole produced marked alterations in tolbutamide kinetics (increased half‐life, decreased clearance). However, if there was substitution in the 2‐ position, irrespective of a substituent on N‐1, then the compound did not appear to inhibit metabolism (e.g. 2‐methylimidazole, 1,2‐dimethylimidazole, methimazole, metronidazole). The 4‐ substituted compounds, 4‐methylimidazole and cimetidine were inhibitors.
A structure‐activity relationship for the inhibitory actions of the substituted imidazoles is thus evident in vivo.
Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo.
The 1‐substituted compounds 1‐methylimidazole, miconazole, clotrimazole and ketoconazole produced marked alterations in tolbutamide kinetics (increased half‐life, decreased clearance). However, if there was substitution in the 2‐ position, irrespective of a substituent on N‐1, then the compound did not appear to inhibit metabolism (e.g. 2‐methylimidazole, 1,2‐dimethylimidazole, methimazole, metronidazole). The 4‐ substituted compounds, 4‐methylimidazole and cimetidine were inhibitors.
A structure‐activity relationship for the inhibitory actions of the substituted imidazoles is thus evident in vivo.
DOI: 10.1111/j.1476-5381.1985.tb08838.x
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