Pharmacokinetic investigation of the interaction of azapropazone with phenytoin.
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.
D000328:Adult; D001032:Apazone / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008297:Male; D010672:Phenytoin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D012463:Saliva / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*
D014227:Triazines; C027364:5-(3-hydroxyphenyl)-5-phenylhydantoin; D010672:Phenytoin; D001032:Apazone