Joomi Lee*, Sook Jin Seong*, Sung Min Park, Jong Gwang Park, Mi-Ri Gwon, Hae Won Lee, Hee-Doo Yoo, Young-Ran Yoon
Clinical Trial Center, Kyungpook National University Hospital, 200 Dongduk-Ro, Jung-gu, Daegu, 700-721, Republic of Korea. Department of Biomedical Science, Kyungpook National University Graduate School, Room 107, 101 Dongin-2 Ga, Jung-gu, Daegu, 700-422, Republic of Korea. BK21 program, Kyungpook National University School of Medicine, 101 Dongin-2ga, Junggu, Daegu 700-422, Republic of Korea. College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University Republic of 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: 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 a NONMEM (Ver. 7.2).
Results: A two-compartment disposition model described the best fit to a total of 728 concentrations. Because absorption kinetics patterns showed double peak, Erlang’s absorption and first-order elimination model were recruited. 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.
Conclusions: A population PK model was developed and reasonable parameters were obtained from the data of healthy Korean male subjects.
[This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2013R1A1A2060131), the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A070001) and the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT& Future Planning, Republic of Korea (NRF-2013M3A9B6046416).]
* Both authors contributed equally to this work
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] Christensen ML, Mottern RK, Jabbour JT, Fuseau E. Pharmacokinetics of sumatriptan nasal spray in children. J Clin Pharmacol. 2004;44(4):359-67.
Reference: PAGE 23 () Abstr 3075 [www.page-meeting.org/?abstract=3075]
Poster: Drug/Disease modeling - Absorption & PBPK