Premium
Dose‐dependent effect of cimetidine on phenytoin kinetics
Author(s) -
Bartle W R,
Walker S E,
Shapero T
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.88
Subject(s) - cimetidine , phenytoin , pharmacology , kinetics , chemistry , medicine , epilepsy , psychiatry , physics , quantum mechanics
Eight normal subjects were given 250 mg intravenous phenytoin alone and with 3‐day regimens of oral Cimetidine, 400 mg at bedtime, 1200 mg a day, and 2400 mg a day in a randomized crossover fashion. Plasma samples for phenytoin and Cimetidine, and urinary concentrations for phenytoin and 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin (HPPH) were measured by HPLC. All Cimetidine regimens decreased phenytoin clearance, and there was no difference between the 400‐mg bedtime dose and the 1200‐mg a day regimens. There was, however, a difference between the 400‐mg and 1200‐mg and the 2400‐mg regimens. There was no linear correlation between steady state Cimetidine plasma concentrations and the decrease in phenytoin clearance. Urinary HPPH/phenytoin ratios decreased with all Cimetidine treatments, but the differences were not significant. Phenytoin toxicity may result when Cimetidine is added to existing regimens of this anticonvulsant. Clinical Pharmacology and Therapeutics (1983) 33, 649–655; doi: 10.1038/clpt.1983.88