We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Population pharmacokinetic analysis of the multiple peaks phenomenon in sumatriptan.
- Authors
Joomi Lee; Mi-sun Lim; Sook Jin Seong; Sung-Min Park; Mi-Ri Gwon; Seunghoon Han; Sung Min Lee; Woomi Kim; Young-Ran Yoon; Hee-Doo Yoo
- Abstract
The objective of this study was to develop a population pharmacokinetic (PK) model for sumatriptan, which frequently shows an atypical absorption profile with multiple peaks. Sumatriptan, a selective agonist for the vascular serotonin (5-HT1) receptor that causes vasoconstriction of the cerebral arteries, is used for the acute treatment of migraine attack with or without aura. Despite its relatively high between-subject variability, few reports have addressed PK modeling of sumatriptan. Plasma data obtained after a single 50-mg oral dose of sumatriptan in 26 healthy Korean male subjects were used. Blood samples were collected 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 h after dosing. Plasma sumatriptan concentrations were analyzed using UPLC/MS/MS. Population PK analysis was performed using plasma concentration data for sumatriptan with NONMEM (ver. 7.2). A total of 364 concentrations of sumatriptan were captured by a one-compartment model with first-order elimination, and a combined transit compartment model and first-order absorption with lag time was successful in describing the PK with multiple peaks in the absorption phase of sumatriptan. The creatinine clearance as a covariate significantly (P < 0.01) influenced the absorption fraction (f ). The final model was validated through a visual predictive check and bootstrapping with no serious model misspecification.
- Subjects
PHARMACOKINETICS; SUMATRIPTAN; SEROTONIN
- Publication
Translational & Clinical Pharmacology, 2015, Vol 23, Issue 2, p66
- ISSN
2289-0882
- Publication type
Article
- DOI
10.12793/tcp.2015.23.2.66