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Inhibition of tolbutamide metabolism by substituted imidazole drugs in vivo : evidence for a structure‐activity relationship
Author(s) -
Back D.J.,
Tjia J.F.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb08838.x
Subject(s) - tolbutamide , in vivo , chemistry , imidazole , pharmacology , metabolism , structure–activity relationship , biochemistry , biology , endocrinology , in vitro , insulin , microbiology and biotechnology
1 Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo . 2 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. 3 A structure‐activity relationship for the inhibitory actions of the substituted imidazoles is thus evident in vivo .