J. Lee,1 S. Seong,1 S. Park,1 M. Gwon,1 Y. Jang,1 H. Lee,1 H. Yoo,2 Y. Yoon1; 1Kyungpook National University Hospital Clinical Trial Center, Daegu, Korea, Republic of, 2College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University Republic of Korea, Kwangju, Korea, Republic of
BACKGROUND: Sumatriptan, a selective agonist for vascular serotonin (5-HT1) receptor causing vasoconstriction of cerebral arteries, is used for the acute treatment of migraine attack with or without aura. Despite its relatively high inter-individual variability, few reports have addressed the pharmacokinetic (PK) modeling of sumatriptan. The aim of this study was to develop a population PK model of sumatriptan in healthy Korean subjects.
METHODS: Plasma data after a single oral dose of 50 mg of sumatriptan in 26 healthy Korean male subjects were used. Blood samples were collected at 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 hours after dosing. Plasma sumatriptan concentrations were analyzed using UPLC/MS/MS. We estimated a population PK analysis of sumatriptan using NONMEM (Ver. 7.2).
RESULTS: A two-compartment model with first-order elimination described the best fit of a total of 312 concentrations. A mixture of zero- and first-order absorption with lag time was successful to describe the PK with multiple peaks in absorption process of sumatritpan. There were no significant covariates affecting PK parameters. The visual predictive check indicated that the PK profile of sumatriptan was adequately described by the proposed population PK model.
CONCLUSION: A population PK model was developed and reasonable parameters were obtained from the data of healthy Korean male subjects.