Clinical Pharmacy section, Department of Pharmacy, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Social Pharmacy and Pharmacy Administration, Faculty of Pharmaceutical Sciences, Burapha University, ChonBuri, Thailand.
J Med Case Rep. 2024 Sep 5;18(1):408. doi: 10.1186/s13256-024-04753-3.
Tacrolimus is a potent calcineurin inhibitor (CNI) that is principally used as a first-line immunosuppressant for the prophylaxis of allograft rejection in liver transplantation (LT) patients. In clinical practice, prescribing the optimal tacrolimus dosage is complicated by its narrow therapeutic index and high pharmacokinetic variability. Thus, performing therapeutic drug monitoring (TDM) of only tacrolimus may not provide optimal drug levels. However, other influential clinical factors affecting tacrolimus levels, such as hemoglobin (Hb), hematocrit, and total bilirubin (TBIL), should be considered while adjusting tacrolimus levels. This case report aims to introduce clinicians and their teams to taking the pharmacokinetic prediction equation into consideration for a better understanding of tacrolimus dosage adjustment during the early postoperative LT.
In this case report, an 18-year-old male patient of Thai ethnicity was admitted for orthotropic liver transplantation, and tacrolimus was prescribed as a cornerstone immunosuppressive agent. In the immediate postoperative period, which is the most challenging period in liver transplantation, the population pharmacokinetics predictive equation was clinically used to assist in dosage adjustment of tacrolimus by considering the significant clinical factors in this case. Hemoglobin and total bilirubin levels were deemed significant clinical factors affecting the oral clearance (CL/F) of tacrolimus. First, a decrease in the Hb concentration increases the free drug concentration and therefore increases the CL/F of tacrolimus. Second, an elevated TBIL decreases the biliary excretion of tacrolimus, resulting in a decrease in the CL/F of tacrolimus. Thus, dose optimization of tacrolimus would be accurate when taking the pharmacokinetic prediction equation into consideration. Moreover, the results may contribute to a better understanding of tacrolimus pharmacokinetic variability in each transplant patient during the immediate postoperative course.
Hemoglobin and total bilirubin were significant clinical factors influencing the oral clearance of tacrolimus early after liver transplantation. A decrease in the hemoglobin concentration would increase the free drug concentration and therefore increase the oral clearance of tacrolimus. An elevated total bilirubin decreases the biliary excretion of tacrolimus, resulting in a decrease in the oral clearance of tacrolimus.
他克莫司是一种强效钙调神经磷酸酶抑制剂（CNI），主要用作肝移植（LT）患者预防同种异体移植物排斥反应的一线免疫抑制剂。在临床实践中，由于其治疗指数狭窄和药代动力学变异性高，因此，仅对他克莫司进行治疗药物监测（TDM）可能无法提供最佳的药物水平。然而，在调整他克莫司水平时，还应考虑影响他克莫司水平的其他有影响的临床因素，如血红蛋白（Hb）、血细胞比容和总胆红素（TBIL）。本病例报告旨在向临床医生及其团队介绍考虑药代动力学预测方程的重要性，以便更好地了解 LT 术后早期他克莫司的剂量调整。
本病例报告介绍了一位 18 岁的泰国男性患者，因接受原位肝移植而入院，他克莫司被用作基石免疫抑制剂。在肝移植的即刻术后期间，即最具挑战性的时期，临床使用群体药代动力学预测方程来协助通过考虑该病例中的重要临床因素来调整他克莫司的剂量。血红蛋白和总胆红素水平被认为是影响他克莫司口服清除率（CL/F）的重要临床因素。首先，血红蛋白浓度降低会增加游离药物浓度，从而增加他克莫司的 CL/F。其次，TBIL 升高会减少他克莫司的胆汁排泄，导致他克莫司的 CL/F 降低。因此，当考虑药代动力学预测方程时，他克莫司的剂量优化将更加准确。此外，结果可能有助于更好地了解每个移植患者在即刻术后期间他克莫司的药代动力学变异性。
血红蛋白和总胆红素是影响肝移植后早期他克莫司口服清除率的重要临床因素。血红蛋白浓度降低会增加游离药物浓度，从而增加他克莫司的口服清除率。TBIL 升高会减少他克莫司的胆汁排泄，导致他克莫司的口服清除率降低。
