Binding of anticonvulsant drugs to cytochrome P-450: correlation with evidence of induction of hepatic microsomal enzymes.
Mephenytoin, diphenylhydantoin, pheneturide, and phenobarbital produced a concentration-dependent inhibition in the binding of hexobarbital to cytochrome P-450 at the type 1 site, while sulthiame slightly potentiated, and ethosuximide did not affect the binding characteristic of hexobarbital. Diphenylhydantoin, phenobarbital, and pheneturide have previously been shown to enhance the urinary excretion of D-glucaric acid (DGA), while sulthiame inhibited the potentiation of DGA excretion caused by these drugs, and ethosuximide produced no change. The results suggest a close relationship between the ability of these drugs to induce hepatic microsomal drug-metabolizing enzyme systems (as indicated by enhancement of DGA excretion) and binding behaviour at the type 1 site.
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005937:Glucaric Acid / Q000652:urine; D006591:Hexobarbital / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008617:Mephenytoin / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D010654:Phenylbutyrates / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives
D000927:Anticonvulsants; D010654:Phenylbutyrates; D011955:Receptors, Drug; D010672:Phenytoin; C005825:pheneturide; D014508:Urea; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D005937:Glucaric Acid; D008617:Mephenytoin; D010634:Phenobarbital