Boram Ohk, Joomi Lee, Sook-Jin Seong,Mi-Ri Gwon, Hae Won Lee, Young-Ran Yoon
Clinical Trial Center, Department of Biomedical Science and BK21 plus program, Kyungpook National University Hospital and School, Daegu, Korea
Objectives: Fimasartan, a novel angiotensin II receptor blocker that has been used for hypertension, is known to have inter-individual pharmacokinetic(PK) variability. The aims of this study were to develop a population PK model of Fimasartan in healthy Korean subjects.
Methods: A randomized, open-label, two-period, crossover bioequivalence study in 49 healthy male adults was performed. All subjects were received either the test or reference formulation as repeated 120-mg oral dose of Fimasartan, followed by a 1-week washout period and administration of the alternate formulation. Blood samples were drawn at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after dosing. Plasma Fimasartan concentrations were analyzed using API 3200. A population PK analysis was conducted using NONMEM (Ver. 7.1).
Results: A 2-compartment model with first-order absorption provided the best fit from healthy subjects. Estimates of the population PK parameter were as follows; CL, 85 L/h; Vc, 350 L; Ka, 5 h-1; Vp, 205 L/h; Q, 25 L/h. The visual predictive check (VPC) was performed and the result exhibited the acceptable predictive performance of the final model.
Conclusions: A population PK model was successfully developed and reasonable parameters were obtained. Further study will be required to find out covariates affecting the PK parameters.
[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).]
References:
Kim S, Lee J, Shin D et al. Effect of renal function on the pharmacokinetics of fimasartan:a single-dose, open-label,Phase 1 study. Drug Design, Development and Therapy 2014;8:1723-1731.
Reference: PAGE 24 (2015) Abstr 3639 [www.page-meeting.org/?abstract=3639]
Poster: Drug/Disease modeling - Other topics