Doxylamine pharmacokinetics following single dose oral administration in children ages 2-17 years
Guhan Balan1, Gary A Thompson, Roger Gibb
1The Procter & Gamble Company, Mason, OH, USA.
Insights
This study characterized doxylamine pharmacokinetics in children aged 2-17 years. Dosing nomograms achieved similar peak drug levels (Cmax) but a modest increase in overall exposure (AUC), with good tolerability.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Drug Metabolism
Background:
- Doxylamine succinate is commonly used in pediatric populations.
- Limited pharmacokinetic data exists for doxylamine in children.
- Understanding age-related drug disposition is crucial for safe and effective pediatric dosing.
Purpose of the Study:
- To characterize the pharmacokinetics of doxylamine in children aged 2-17 years.
- To assess the impact of age and weight on doxylamine pharmacokinetics.
- To evaluate the safety and tolerability of doxylamine in this pediatric cohort.
Main Methods:
- A single oral dose of doxylamine succinate was administered to 41 children (ages 2-17).
- Plasma samples were collected over 72 hours post-dose for doxylamine analysis using HPLC MS/MS.
- Pharmacokinetic parameters were estimated using non-compartmental analysis and linear regression for age-related trends.
Main Results:
- Maximum drug concentration (Cmax) was similar across a fourfold dose range, while area under the curve (AUC) showed a non-significant 60% increase.
- Clearance (CLo) and volume of distribution (Vz/F) increased with age, consistent with body size changes.
- Elimination half-life (t1/2,z) remained stable around 16 hours, and no significant age-related maturation effects on clearance were observed.
Conclusions:
- Age- and weight-based dosing nomograms for doxylamine in children result in comparable Cmax with a modest increase in AUC.
- Doxylamine demonstrated good tolerability in pediatric subjects, with somnolence being the most frequent adverse event.
- Pharmacokinetic parameters like clearance and volume of distribution are influenced by age and body size in children, but half-life remains consistent.
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%.
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