POPULATION PHARMACOKINETICS OF TACROLIMUS IN THAI LIVER TRANSPLANT PATIENTS

Authors

  • Vichapat Tharanon
  • Abhasnee Sobhonslidsuk
  • Pongphob Intaraprasong
  • Supasil Sra-ium
  • Bundit Sakulchairungrueng Division of Vascular and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok
  • Goraguch Gesprasert Division of Vascular and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok
  • Nuttapon Arpornsujaritkun Division of Vascular and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok
  • Surasak Leelaudomlipi Division of Vascular and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok
  • Suthus Sriphojanart Division of Vascular and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok
  • Thitima Wattanavijitkul Chulalongkorn University

DOI:

https://doi.org/10.69598/tbps.16.1.17-30

Keywords:

population pharmacokinetics, tacrolimus, liver transplant patients

Abstract

Tacrolimus is a highly effective immunosuppressant but has a narrow therapeutic index with high pharmacokinetic variability. This study aimed to characterize the population pharmacokinetics of tacrolimus and to explore clinical factors that could explain the pharmacokinetic variability of tacrolimus during the 8th day to the 6th month after liver transplantation. A total of 1,012 tacrolimus concentration-time measurements from 50 recipients receiving oral immediate-release tacrolimus were analyzed by nonlinear mixed effects approach using NONMEM. In addition, thirteen clinical covariates including body weight, hemoglobin (HB), hematocrit (HCT), liver function tests (AST, ALT, ALP, GGT, TB, DB), renal function tests (BUN, SCr), albumin and a number of post-operative days were tested to explore their influential effects on the pharmacokinetic variability. It was found that pharmacokinetic properties of tacrolimus were best described by a one-compartment model with first order absorption and elimination. HB and total bilirubin (TB) significantly affected the oral clearance (CL/F) of tacrolimus. Increased levels of HB or TB would result in a decrease in the CL/F of tacrolimus as indicated in the following equation. CL/F = 26.2 x (HB/11)–0.802 x (TB/1.9)–0.096 L/h. None of the tested clinical factors were found to significantly influence the apparent volume of distribution of tacrolimus. This finding suggests that HB and TB are significant factors influencing the CL/F of tacrolimus in Thai liver transplant patients. Therefore, these two clinical factors should be considered in determining the tacrolimus dosage during the first 6 months’ post-transplantation.

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Published

2021-03-02

How to Cite

Tharanon, V. ., Sobhonslidsuk, A. ., Intaraprasong, P., Sra-ium, S., Sakulchairungrueng, B. ., Gesprasert, G. ., Arpornsujaritkun, N. ., Leelaudomlipi, S., Sriphojanart, S. ., & Wattanavijitkul, T. (2021). POPULATION PHARMACOKINETICS OF TACROLIMUS IN THAI LIVER TRANSPLANT PATIENTS. Thai Bulletin of Pharmaceutical Sciences, 16(1), 17–30. https://doi.org/10.69598/tbps.16.1.17-30

Issue

Vol. 16 No. 1 (2021): JANUARY - JUNE 2021

Section

Original Research Articles

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