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Effects of inducers and inhibitors of mixed‐function oxidases on the biliary excretion of pentacaine metabolites
Author(s) -
Kukan M.,
Bezek Š.,
Ščasnár V.,
Ďurišová M.,
Trnovec T.
Publication year - 1990
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510110504
Subject(s) - excretion , metabolite , phenobarbital , chemistry , medicine , endocrinology , methylcholanthrene , metabolism , pharmacology , biology , biochemistry , carcinogen
The biliary excretion of 3 H‐pentacaine and its metabolites was studied in rats pretreated with an inducer or inhibitor of mixed‐function oxidases. Over one‐fourth (25·8 per cent) of a 2 mg kg −1 intraportal dose of 3 H‐pentacaine was excreted in bile in urethaneanaesthetized control rats within 3 h. The radioactivity appeared in the form of the parent drug, basic metabolites, and metabolite conjugates, 3·1, 86·5, and 10·4 per cent of the total radioactivity excreted, respectively. Pretreatment of rats with phenobarbital enhanced only slightly the biliary excretion of basic metabolites, and pretreatment with 3‐methylcholanthrene had no effect. Phenobarbital also increased the initial rate of excretion of conjugates, but this effect was not sustained. 3‐Methylcholanthrene had a tendency to impair excretion of conjugates by bile. Pretreatment of rats with SKF 525‐A decreased the biliary excretion of both basic metabolites and conjugates while cimetidine did not alter significantly the biliary excretion of pentacaine metabolites. These results suggest that the canalicular transport of metabolites may be the most important factor in controlling pentacaine metabolite excretion in bile.