Absence of pharmacokinetic interaction between orally co-administered naproxen sodium and diphenhydramine hydrochloride

The potential for a pharmacokinetic interaction between naproxen and diphen hydramine was examined in a randomized three-way crossover design with a 1- week washout between dosing. Single oral doses of 220 mg of naproxen sodium and 50 mg of diphenhydramine hydrochloride were given separately and toget her to 30 healthy male and female subjects. Heparinized blood samples obtai ned for 48 h postdose were assayed for plasma naproxen and diphenhydramine concentrations using validated high-performance liquid chromatography (HPLC ) and gas chromatography (GC) assay methods, respectively. The area under t he plasma concentration-time curve (AUC), maximum plasma concentrations (C- max), time of C-max (T-max) and terminal exponential half-life (t(1.2,z)), were analysed for significant treatment differences by analysis of variance (ANOVA). Based on absence of significant treatment effects on AUC and C-ma x, single-dose oral co-administration of 220 mg of naproxen sodium with 50 mg of diphenhydramine hydrochloride does not alter the pharmacokinetics of either naproxen or diphenhydramine. Significant treatment differences seen for naproxen T-max (0.3 h, males only) and diphenhydramine t(1.2,z) (0.8 h, females only) were minor and are unlikely to have therapeutic consequences . Thus, efficacy and safety of concomitant naproxen and diphenhydramine sho uld not be altered due to a pharmacokinetic interaction. Copyright (C) 2000 John Wiley & Sons, Ltd.