Joomi Lee1,2, Sung Min Park1,2, Mi-sun Lim1,2, Sook-Jin Seong1,2, Jeonghyeon Park1,2, Jeong Ju Seo1,2, Seunghoon Han3, Hae Won Lee1,Young-Ran Yoon1,2
1 Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu, Korea 2 Brain Korea 21 Program, Kyungpook National University School of Medicine, Daegu, Korea 3 Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, Korea
Objectives: 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: A randomized, two-period, crossover bioequivalence study was performed in 26 healthy Korean male subjects. All subjects were received either the test or reference formulation as a single 50-mg oral dose of sumatriptan succinate with a 1-week washout period. 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. A population PK analysis was performed using plasma concentration data from both formulations through NONMEM (Ver. 7.2).
Results: A one-compartment disposition model described the best fit to a total of 728 concentrations. Because absorption kinetics patterns showed double peak, parallel first-order absorption and numerical transit compartment model were recruited. There were no significant covariates affecting PK parameters. The one-compartment structural model was validated through the visual predictive check (VPC) and bootstrap with no serious model misspecification.
Conclusions: A population PK model was developed and reasonable parameters were obtained from the data of healthy Korean male subjects.
References:
[1] Cosson VF, Fuseau E. Mixed effect modeling of sumatriptan pharmacokinetics during drug development: II. From healthy subjects to phase 2 dose ranging in patients. J Pharmacokinet Biopharm 1999;27(2):149-71.
[2]Savic RM, Jonker DM, Kerbusch T, Karlsson MO. Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies. J Pharmacokinet Pharmacodyn 2007;34:711-26.
(This research was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A070001))
Reference: PAGE 21 () Abstr 2489 [www.page-meeting.org/?abstract=2489]
Poster: Model evaluation