A Comparison of the Pharmacokinetics and Tolerability of the Anti-Migraine Compound Almotriptan in Healthy Adolescents and Adults

Abstract

This study was designed to assess and compare the pharmacokinetics and tolerability of almotriptan, a 5-HT1B/1D agonist used to treat migraine attacks, in adolescents and adults. Healthy adolescents (n = 18) and adults (n = 18) received a single 12.5-mg dose of almotriptan after fasting overnight. Plasma and urinary almotriptan concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters of almotriptan were determined by non-compartment analysis. The 90% confidence interval (CI) approach was employed to assess age effects. Mean Cmax, tmax, area under the curve (AUC0- infinity ), half-life, and percentage excreted in urine were nearly identical for the two populations. Mean oral (CLPO) and renal (CLR) clearances were similar between the age groups; however, weight-corrected CLPO was approximately 32% higher (90% CI 16, 51) in adolescents compared with adults. The higher weight-corrected CLPO appeared to offset increases in exposure expected on the basis of lower body weight in adolescents. The findings were the same when a subgroup (n = 9) of 12-14-year-old children was compared with adults. The type, incidence and severity of adverse events were similar between the two age groups and were consistent with those reported previously during adult clinical trials. Based on these pharmacokinetic and tolerability findings, no dose adjustment for almotriptan would be required when treating patients as young as 12 years old.

Almotriptan: a review of 20 years’ clinical experience

“…ALT shows little potential for clinically relevant pharmacokinetic drug interactions [23][24][25][26][27][28]. No dose adjustments are required based on age or gender [15,29]. The clearance of ALT is reduced in severe renal impairment and consequently the dosage should not exceed 12.5 mg/day in such patients [15].…”

LC–ESI-MS/MS determination of in vivo metabolites of almotriptan in rat plasma, urine and feces: Application to pharmacokinetics

“…The LC with UV methods were found to be less sensitive to study the metabolites in plasma, urine and feces [13][14][15][16][17][18][19]. Aubets et al have studied the disposition and metabolism of almotriptan in rats, dogs and monkeys [20].…”

Pharmacokinetics and Tolerability of Rizatriptan in Pediatric Migraineurs in a Randomized Study

“…Supporting pharmacokinetic data were not provided. Previous pharmacokinetic studies of sumatriptan 20‐mg nasal spray and almotriptan 12.5‐mg tablets in adolescents >12 years old found similar pharmacokinetics to adults 10,11 . A study of sumatriptan nasal spray in children 6‐11 years old found that a dosing scheme based on age and weight resulted in comparable pharmacokinetics to those observed in adolescents and adults treated with 20 mg 12 …”

“…Previous pharmacokinetic studies of sumatriptan 20-mg nasal spray and almotriptan 12.5-mg tablets in adolescents >12 years old found similar pharmacokinetics to adults. 10,11 A study of sumatriptan nasal spray in children 6-11 years old found that a dosing scheme based on age and weight resulted in comparable pharmacokinetics to those observed in adolescents and adults treated with 20 mg. 12 The current study evaluated, in pediatric migraineurs aged 6 to 17 years, the pharmacokinetics of the weight-based rizatriptan dosing regimen previously utilized by Ahonen et al 9 Children weighing <40 kg received a single dose of rizatriptan oral disintegrating tablet (ODT) 5 mg, and those weighing Ն40 kg received a single dose of rizatriptan ODT 10 mg. This is the first report of the pharmacokinetics of rizatriptan in children using a weight-based dosing regimen.…”