Pharmacokinetics of sumatriptan nasal spray in children.

ABSTRACT

The authors studied the pharmacokinetics of sumatriptan nasal spray after a single dose in children migraineurs outside of migraine attack. Seventeen subjects (9 females) ages 6 to 11 years were given one dose of sumatriptan nasal spray based on age and weight; children 6 to 8 years of age weighing children ages 6 to 8 years weighing > 25 kg and children ages 9 to 11 years of age weighing children ages 9 to 11 years weighing > 40 kg received 20 mg (n = 4). Plasma sumatriptan concentrations were determined in serial blood samples obtained over 8 hours. Pharmacokinetic analysis included both noncompartmental and population modeling methods. The pharmacokinetic parameter estimates (geometric mean [95% confidence interval]) following 5, 10, and 20 mg sumatriptan were, respectively, as follows maximum concentration = 8.1 ng/mL (3.6-18.4), 10.8 ng/mL (7.7-15.4), and 12.3 ng/mL (7.6-19.9); half-life = 1.4 hours (1.2-1.8), 1.7 hours (1.4-2.0), and 1.7 hours (1.3-2.3); and AUC = 27.8 ng*h/mL (9.7-79.8), 42.4 ng*h/mL (30.6-58.8), and 49.2 ng*h/mL (32.9-73.7). The median time to maximum concentration for all groups was 2 hours. Population pharmacokinetic modeling included pooled data from this study and from an adolescent study (n = 16). Clearance (CL/F) was 197 L/h for a 30-kg child with between-subject variability of 28%, and the volume of distribution was 751 L, normalized for an 11-year-old child with variability of 43%. The covariate analysis showed that volume increases with age and clearance increases with body size. The absorption was complex, often displaying double-peak plasma concentrations, with a rapid absorption phase and a delayed and rate-limited absorption phase. The dosing scheme based on age and weight resulted in maximal concentrations (C(max)) and systemic exposure (AUC) that were comparable to those observed in adolescents and adults treated with 20 mg. The age- and weight-adjusted dosing scheme appears to an appropriate initial dosing regimen for children with migraine headache. Appropriate safety and efficacy trials will need to be completed in children prior to recommending its use in children.