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Doxylamine pharmacokinetics following single dose oral administration in children ages 2–17 years


Corresponding author:

Guhan Balan, PhD, MBA, The Procter & Gamble Company, 8700 Mason Montgomery Road, Mason, OH 45040, USA



To characterize doxylamine pharmacokinetics in children. This study was conducted in 41 subjects, ages 2–17 years. Doxylamine succinate doses based on age/weight ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz. of water or decaffeinated beverages ∼2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed for doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non-compartmental methods and relationships with age were assessed using linear regression. Over the fourfold dose range, Cmax was similar while AUC increased only 60%, although not statistically significant (P-value = 0.0517). As expected due to increasing body size, CLo and Vz/F increased with age. Due to a similar increase with age for Clo and Vz/F, no age-related differences in t1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CLo; although Vz/F remained age-dependent, the predicted range decreased ∼70%. Overall, the single doses were well tolerated. Somnolence was the most common reported AE with no apparent differences in incidence noted with age. An age/weight dosing nomogram utilizing a fourfold range of doses achieves similar Cmax, whereas AUC increases only 60%.