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POPULATION PHARMACOKINETICS OF TACROLIMUS IN THAI LIVER TRANSPLANT PATIENTS |
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| รหัสดีโอไอ | |
| Creator | Thitima Wattanavijitkul |
| Title | POPULATION PHARMACOKINETICS OF TACROLIMUS IN THAI LIVER TRANSPLANT PATIENTS |
| Contributor | Vichapat Tharanon, Abhasnee Sobhonslidsuk, Pongphob Intaraprasong, Supasil Sra-ium,Bundit Sakulchairungrueng, Goraguch Gesprasert, Nuttapon Arpornsujaritkun,Surasak Leelaudomlipi, Suthus Sriphojanart |
| Publisher | Faculty of pharmacy, Silpakorn University |
| Publication Year | 2564 |
| Journal Title | Thai Bulletin of Pharmaceutical Sciences |
| Journal Vol. | 16 |
| Journal No. | 2(July-December)2021 |
| Page no. | 17-30 |
| Keyword | population pharmacokinetics, tacrolimus, liver transplant patients |
| URL Website | https://li01.tci-thaijo.org/index.php/TBPS |
| ISSN | 2586-8659 |
| 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. |
