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Doxylamine pharmacokinetics following single dose oral administration in children ages 2–17 years
Author(s) -
Balan Guhan,
Thompson Gary A.,
Gibb Roger,
Li Lijuan,
Hull David,
Seeck Molly
Publication year - 2013
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.137
Subject(s) - pharmacokinetics , cmax , dosing , medicine , oral administration , bioavailability , nomogram , pharmacology
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 max was similar while AUC increased only 60%, although not statistically significant ( P ‐value = 0.0517). As expected due to increasing body size, CL o and V z /F increased with age. Due to a similar increase with age for Cl o and V z /F, no age‐related differences in t 1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CL o ; although V z /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 max , whereas AUC increases only 60%.