Single‐Dose Pharmacokinetic Study of Diphenhydramine HCl in Children and Adolescents

Diphenhydramine pharmacokinetics were characterized following a single oral dose in children aged 2 to 17 years using a weight‐ and age‐based dosing schedule with more tiers than the current age‐based dosing schedule recommended by the nonprescription drug monograph. This study was conducted in 42 subjects, aged 2 to 17 years. Doses were based on a weight‐age dosing schedule, ranging from 6.25 to 50 mg. An oral dose was administered with water about 2 hours after a light breakfast. Plasma samples were obtained up to 48 hours after dosing and analyzed for diphenhydramine. Pharmacokinetic parameters were estimated using noncompartmental methods, and the relationship of oral clearance with age was assessed using linear regression. Over an 8‐fold range of doses, Cmax and AUC increased ∼90 % to ∼140% across age groups, with a similar Tmax (1.5 hours). Oral CL/F increased with age, but after allometric scaling, no maturation‐related change in CL/F was apparent. Mild somnolence was the most commonly reported adverse event (95% of the subjects). A weight‐age dosing schedule using an 8‐fold range of doses achieved Cmax and AUC that increased about 2‐fold across age groups. No effect of maturation on CL/F was observed after allometric scaling.