A comparison of the pharmacokinetics and tolerability of the anti-migraine compound almotriptan in healthy adolescents and adults.
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.
Baldwin
J R
JR
Department of Clinical Pharmacology, Pharmacia, Kalamazoo, MI 49001, USA. john.r.baldwin@pharmacia.com
Fleishaker
J C
JC
Azie
N E
NE
Carel
B J
BJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019540:Area Under Curve; D002648:Child; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D017366:Serotonin Receptor Agonists / Q000009:adverse effects* / Q000032:analysis / Q000493:pharmacokinetics*; D014363:Tryptamines
D007211:Indoles; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan