title: Doxylamine pharmacokinetics following single dose oral administration in children ages 2-17 years.
abstract: 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%.
authors.affiliation: The Procter & Gamble Company, Mason, OH, USA.
authors.forename: Guhan
authors.initials: G
authors.lastname: Balan
authors.forename: Gary A
authors.initials: GA
authors.lastname: Thompson
authors.forename: Roger
authors.initials: R
authors.lastname: Gibb
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Hull
authors.forename: Molly
authors.initials: M
authors.lastname: Seeck
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004319:Doxylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male
chemical_list: D006634:Histamine H1 Antagonists; D004319:Doxylamine; C035385:doxylamine succinate
keywords: doxylamine; over-the-counter (OTC); pediatrics; pharmacokinetics