Doxylamine pharmacokinetics following single dose oral administration in children ages 2–17 years1. (18th July 2013)

• Record Type: Journal Article
• Authors: Balan, Guhan; Thompson, Gary A.; Gibb, Roger; Li, Lijuan; Hull, David; Seeck, Molly
• Is Part Of: Journal of clinical pharmacology. Volume 53:Number 11(2013:Nov.)
• Page Start: 1177
• Page End: 1185
• Publication Date: 2013-07-18
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.137
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph137-sec-0001" sec-type="section"> <p>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, C<sub>max</sub> was similar while AUC increased only 60%, although not statistically significant (<italic>P</italic>‐value = 0.0517). As expected due to increasing body size, CL<sub>o</sub> and V<sub>z</sub>/F increased with age. Due to a similar increase with age for Cl<sub>o</sub> and V<sub>z</sub>/F, no age‐related differences in t<sub>1/2, z</sub> were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CL<sub>o</sub>; although V<sub>z</sub>/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 C<sub>max</sub>, whereas AUC increases only 60%.</p> </sec> </abstract>