Pharmacokinetics of diphenhydramine in healthy volunteers with adimenhydrinate 25 mg chewing gum formulation

Abstract

This pharmacokinetic study evaluated diphenhydramine in the plasma of healthy volunteers after a single 25 mg oral dose of dimenhydrinate (diphenhydramine theophyllinate), corresponding to 12.7 mg diphenhydramine, in a chewing gum formulation. Seven volunteers (4 men, 3 women; age: 26.3 ± 1.2 years; body weight: 63.1 ± 4.1 kg; height: 172.4 ± 4.6 cm) chewed the gum for 1 h. Blood samples (10 ml) were collected at different time intervals up to 24 h. Blood plasma was subsequently processed and analyzed for diphenhydramine content using a GLC method and an NPD detector. Analytical data revealed the following kinetic parameters: AUC0-24h: 155.2h x ng x ml-1; AUC0-infinite: 195.3 h x ng x ml-1; Mean resident time: 16 h; t1/2: 10 h; Cmax: 14.5 ng x ml-1; tmax: 2.6 h; and plasma clearance: 9.0 ml x min-1 x kg-1. This study indicates that the pharmaceutical formulation employed provided sustained plasma concentrations of diphenhydramine, presumably sufficient to support its clinical efficacy towards motion sickness owing to the almost complete (> 95%) release by the formulation of the active principle. Moreover, the maximal concentrations of diphenhydramine attained in plasma were much lower than the concentration threshold needed to produce drowsiness.