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Pharmacokinetic investigation of the interaction of azapropazone with phenytoin.
Author(s) -
Geaney DP,
Carver JG,
Davies CL,
Aronson JK
Publication year - 1983
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1983.tb01557.x
Subject(s) - phenytoin , pharmacokinetics , pharmacology , chemistry , drug interaction , plasma concentration , hydroxylation , pharmacokinetic interaction , medicine , biochemistry , epilepsy , enzyme , psychiatry
We have investigated the interaction of azapropazone with phenytoin in five healthy volunteers. From steady‐state plasma phenytoin concentrations of about 17 mumol/l there was at least a two‐fold increase following the introduction of azapropazone. The main mechanism of the interaction was a decrease in phenytoin clearance, attributable to competitive inhibition by azapropazone of phenytoin p‐hydroxylation. Protein‐binding of phenytoin in the plasma (as assessed by salivary phenytoin concentrations) was significantly reduced from 92 to 90% by azapropazone and similar changes occurred in in vitro studies of [3H]‐ phenytoin protein binding.