Boram Ohk, Joomi Lee, Mi-Ri Gwon, Bo Kyung Kim, Hae Won Lee,Hyun-Ju Kim, Sook Jin Seong, Woo Youl Kang and Young-Ran Yoon
Dep. of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent and Clinical Trial Center,
Objectives: Tacrolimus, an immunosuppressive agent that has been commonly used to prevent rejection after organ transplantation, is known to have substantial inter-individual pharmacokinetic (PK) variability and narrow therapeutic range. Tacrolimus is primarily metabolized by the cytochrome P450 enzymes CYP3A4 and CYP3A5. Differences in activity of metabolizing enzymes are responsible for a large part of the variability in pharmacokinetics. The aim of this study was to develop a population PK model of tacrolimus in healthy Korean subjects.
Methods: This study was conducted in 29 healthy Korean subjects. All received 0.075mg/kg oral dose of tacrolimus. Blood samples were drawn at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after dosing. Plasma tacrolimus concentrations were analyzed using liquid chromatography mass spectrometry (LC/MS). A population PK analysis was conducted using NONMEM (Ver. 7.2).
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, 12.5 L/h; Vc, 19.6 L; Ka, 0.545 h-1; ALAG, 0.363 h; Vp, 359 L; Q, 26.4 L/h. The visual predictive check (VPC) was performed and the result exhibited the acceptable predictive performance of the final model.
Conclusions: The 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 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), by the Industrial Core Technology Development Program (10051129, Development of the system for ADME assessment using radiolabeled compounds) funded by the Ministry of Trade, Industry & Energy, by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2750,HI15C0001).]
Reference: PAGE 25 () Abstr 5860 [www.page-meeting.org/?abstract=5860]
Poster: Drug/Disease modeling - Other topics