A comparison of the influence of famotidine and cimetidine on phenytoin elimination and hepatic blood flow.
The H2-receptor antagonist cimetidine has been reported to decrease the hepatic clearance of numerous drugs by inhibiting cytochrome P-450 metabolism, decreasing liver blood flow or both. In this open-label, randomized crossover study we determined whether therapeutic doses of famotidine, a newer H2-receptor antagonist, has similar effects. Ten healthy subjects received single doses of both phenytoin 100 mg orally and indocyanine green intravenously without other treatment, and then again during treatment with famotidine or cimetidine. After a drug-free period, this sequence was repeated with the alternate H2-receptor antagonist. Cimetidine decreased the plasma clearance of phenytoin by 16% +/- 14% (mean +/- s.d.), but was not found to have a significant influence on phenytoin volume of distribution or terminal elimination rate constant nor on blood clearance of indocyanine green. Famotidine was not found to alter either phenytoin or indocyanine green kinetics.
Sambol
N C
NC
Department of Pharmacy, School of Pharmacy, University of California, San Francisco.
Upton
R A
RA
Chremos
A N
AN
Lin
E T
ET
Williams
R L
RL
D002927:Cimetidine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004341:Drug Evaluation; D015738:Famotidine; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D010672:Phenytoin / Q000493:pharmacokinetics*; D011897:Random Allocation; D013844:Thiazoles / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D013844:Thiazoles; D015738:Famotidine; D010672:Phenytoin; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D007208:Indocyanine Green