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Population Pharmacokinetic Analysis of Zolmitriptan and Its Metabolite in Adults and Adolescents to Support Dose Selection in Children With Migraine.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2017 Oct; Vol. 57 (10), pp. 1258-1267. Date of Electronic Publication: 2017 Jun 05. - Publication Year :
- 2017
-
Abstract
- Zolmitriptan is a serotonin (5-HT) <subscript>1B/1D</subscript> receptor agonist effective for the treatment of migraine. This analysis aimed to develop a population pharmacokinetic (PK) model for zolmitriptan and its active metabolite in adults and adolescents and provide appropriate dosing regimens to be used in clinical trials for children 6-11 years old. The data from a single-dose clinical study of 5.0-mg zolmitriptan nasal spray (ZNS) conducted in adult and adolescent patients with migraine between migraine attacks was applied. Similar plasma concentration profiles of zolmitriptan and its metabolite, 183C91, were observed in adults and adolescents. A 1-compartment model with first-order absorption and first-order elimination reasonably described the zolmitriptan PK. With a portion of elimination of zolmitriptan being treated as the conversion from zolmitriptan to 183C91, the disposition of 183C91 was described by a 1-compartment model with first-order elimination. The estimated typical apparent volume of distribution and clearance of zolmitriptan were 136 L and 121 L/h, respectively, with 56.5% and 42.6% between-subject variability, respectively. Based on the simulation results with the final population PK model, a body weight-based dosing scheme of 5.0 and 2.5 mg ZNS in children greater than and less than 50 kg is recommended to achieve exposures similar to those of the adult and adolescent population administered 5.0 mg ZNS. The recommended doses for children to achieve exposure similar to that observed in adults given 2.5 mg ZNS are 2.5 mg (≥50 kg) and 1.0 mg (15-50 kg). These dosing regimens could be used in future clinical trials.<br /> (© 2017, The American College of Clinical Pharmacology.)
- Subjects :
- Administration, Intranasal
Adolescent
Adult
Body Weight
Child
Dose-Response Relationship, Drug
Female
Humans
Male
Middle Aged
Migraine Disorders blood
Migraine Disorders drug therapy
Migraine Disorders metabolism
Oxazoles blood
Oxazolidinones blood
Oxazolidinones therapeutic use
Serotonin 5-HT1 Receptor Agonists blood
Serotonin 5-HT1 Receptor Agonists therapeutic use
Tryptamines blood
Tryptamines therapeutic use
Young Adult
Models, Biological
Oxazolidinones administration & dosage
Oxazolidinones pharmacokinetics
Serotonin 5-HT1 Receptor Agonists administration & dosage
Serotonin 5-HT1 Receptor Agonists pharmacokinetics
Tryptamines administration & dosage
Tryptamines pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 57
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28581633
- Full Text :
- https://doi.org/10.1002/jcph.935