Transl Clin Pharmacol.  2015 Dec;23(2):66-74. 10.12793/tcp.2015.23.2.66.

Population pharmacokinetic analysis of the multiple peaks phenomenon in sumatriptan

Affiliations
  • 1Clinical Trial Center, Department of Biomedical Science and BK21 Plus Program, Kyungpook National University Hospital and School, Daegu 41944, Republic of Korea.
  • 2College of Pharmacy, Yeungnam University, Gyeongsan 42415, Korea.
  • 3PIPET (Pharmacometrics Institute for Practical Education and Training), The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • 4Department of Pharmacology, Kosin University College of Medicine, Busan 49267, Korea.
  • 5Department of Biostatistics and Bioinformatics, Pharma Partnering Inc., Seoul 06735, Republic of Korea. yooheedoo@gmail.com

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.

Keyword

Multiple peaks phenomenon; NONMEM; population pharmacokinetics; sumatriptan

MeSH Terms

Absorption
Cerebral Arteries
Creatinine
Epilepsy
Humans
Male
Migraine Disorders
Plasma
Serotonin
Sumatriptan*
Vasoconstriction
Creatinine
Serotonin
Sumatriptan
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