Pharmacokinetics and tolerability of rizatriptan in pediatric migraineurs in a randomized study.

Objective. To evaluate the pharmacokinetic profile and tolerability of single doses of rizatriptan oral disintegrating tablets (ODTs) in pediatric migraineurs. Background.-Acute migraine treatment options for children are limited despite a rising migraine prevalence. No triptans are approved in those under 12, and only sumatriptan nasal spray (European Union) and almotriptan tablets (USA) are approved for those aged 12-17. Appropriate dose selection based on body weight may be a factor in establishing treatment efficacy in this population. Methods.-Randomized, double-blind, placebo-controlled, parallel group, single-dose study in 6-to 17-year-old migraineurs. The study was performed between acute migraine attacks. Subjects were allocated to 1 of 2 groups based on body weight: (1) those weighing < 40 kg received rizatriptan ODT 5 mg or placebo; (2) those weighing 40 kg received rizatriptan 10 mg ODT or placebo. Pharmacokinetic data were compared with historical data on rizatriptan ODT 10 mg in healthy adults. Results.-The geometric mean area under the plasma concentration-time curve from time 0 to infinity (AUC(0-)) (hours u ng/mL) and maximum peak plasma concentration (Cmax) (ng/mL) were 56.68 (95% confidence interval [ CI]: 48.60, 66.09) and 22.39 (95% CI: 17.90, 28.02), respectively, for the < 40 kg group and 78.49 (95% CI: 68.93, 89.38) and 22.27 (95% CI: 18.43, 26.92), respectively, for the 40 kg group. For the comparison of children vs adults, the geometric mean ratios for rizatriptan AUC(0-) and Cmax were 0.85 (90% CI: 0.73, 0.98) and 1.07 (90% CI: 0.86, 1.34), respectively, for the < 40 kg group vs historical adult data and 1.17 (90% CI: 1.02, 1.34) and 1.06 (90% CI: 0.87, 1.30), respectively, for the 40 kg group vs historical adult data. There were no serious adverse events, and rizatriptan was generally well tolerated. Conclusions.-In pediatric migraineurs, a weight-based dosing scheme generated plasma rizatriptan AUC(0-) and Cmax values that were generally similar to those historically observed in adults administered a 10-mg dose of rizatriptan ODT (a proven effective dose). The data support further evaluation of the safety, tolerability, and efficacy of this rizatriptan dosing scheme in larger scale clinical trials in the pediatric migraineur population.