Single-Dose Pharmacokinetics and Metabolism of the Oral Decongestant Phenylephrine HCl in Children and Adolescents

INTRODUCTION: Pediatric data for phenylephrine, a decongestant used in cold medicines, are limited. This study characterized the pharmacokinetics and metabolism of phenylephrine HCl in children aged 2–17 years. METHODS: Forty-one children experiencing nasal congestion were dosed orally with phenylephrine HCl from 2.5 to 10 mg using a modified weight–age schedule. Plasma from blood samples collected up to 4.5 h after dosing was analyzed for phenylephrine. Urine collected over 24 h was analyzed for phenylephrine and metabolites. Blood pressure and pulse were measured after each blood sampling, and electrocardiograms were recorded before and after dosing. Pharmacokinetic parameters were estimated using noncompartmental methods. RESULTS: Mean phenylephrine total exposure (AUC(∞)) for children aged 2–5, 6–11, and 12–17 years was 672, 830, and 1020 pg∙h/mL, and mean maximum concentration (C(max)) was 477, 589, and 673 pg/mL, respectively. Times to peak concentration (T(max)) ranged from 0.17 to 1.5 h, and elimination half-life (t(½,β)) was short from 1.2 to 1.6 h. Oral clearance (CL/F) increased with age, but with allometric scaling for body size, this trend reversed as scaled clearance (CL/F,(scaled)) was modestly higher in youngest children. No clinically relevant changes in vital signs or electrocardiograms were observed. CONCLUSION: A dosing schedule with additional weight–age increments would provide more consistent systemic concentrations as children age and receive the next higher dose. No developmental delays in clearance mechanisms were apparent when oral clearance was scaled for body size. Phenylephrine pharmacokinetics and metabolism were consistent with adult data, although AUC∞ for the youngest group and C(max) for all pediatric groups were lower. Single doses of phenylephrine HCl were well tolerated. TRIAL REGISTRATION: Clintrials.gov NCT00762567, registered 30 September 2008.