Pharmacokinetics of diphenhydramine in healthy volunteers with a dimenhydrinate 25 mg chewing gum formulation.
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: AUC(0-24h): 155.2h x ng x ml(-1); AUC(0-infinity): 195.3 h x ng x ml(-1); Mean resident time: 16 h; t(1/2): 10 h; C(max): 14.5 ng x ml(-1); t(max): 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.
Valoti
M
M
Centro Interdisciplinare di Ricerca sul Metabolismo dei Farmaci Neuropsicotropi, Istituto di Scienze Farmacologiche, Universita di Siena, Siena, Italy. valoti@unisi.it
Frosini
M
M
Dragoni
S
S
Fusi
F
F
Sgaragli
G
G
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002638:Chewing Gum; D002849:Chromatography, Gas; D004111:Dimenhydrinate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004155:Diphenhydramine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate
D002638:Chewing Gum; D006634:Histamine H1 Antagonists; D004155:Diphenhydramine; D004111:Dimenhydrinate