Lack of pharmacokinetic interaction between lansoprazole and intravenously administered phenytoin.
The objective of this randomized, double-blind, two-period crossover study was to investigate whether concomitant steady-state lansoprazole influences the pharmacokinetics of CYP2C9 substrates using single intravenously dosed phenytoin as a model substrate. In addition, the safety of concomitant administration of these two drugs was evaluated. Twelve healthy, nonsmoking, adult male subjects received 60 mg lansoprazole or placebo once daily for 9 days during each study period. On the morning of day 7, each subject received a single 250 mg intravenous phenytoin dose. There were no statistically significant differences between the two regimens for mean phenytoin Cmax or tmax. There was a minor (< 3%) but statistically significant difference between the two regimens for phenytoin AUC resulting from a very low intrasubject coefficient of variation (2.3%). The treatment and control mean plasma concentration phenytoin profiles were virtually super-imposable. In conclusion, concomitant multidose lansoprazole administration is unlikely to have any clinically significant effect on the pharmacokinetics of CYP2C9 substrates in general or intravenous phenytoin specifically.
Karol
M D
MD
Abbott Laboratories, Abbott Park, Illinois 60064-6104, USA.
Locke
C S
CS
Cavanaugh
J H
JH
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D007275:Injections, Intravenous; D064747:Lansoprazole; D008297:Male; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D010672:Phenytoin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000927:Anticonvulsants; C400322:cytochrome P-450 CYP2C subfamily; D064747:Lansoprazole; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D009853:Omeprazole