背景:他克莫司是一种有效的钙调磷酸酶抑制剂(CNI),主要用作一线免疫抑制剂,用于预防肝移植(LT)患者的同种异体移植排斥反应。在临床实践中,他克莫司的最佳剂量处方因其狭窄的治疗指数和高的药代动力学变异性而复杂化。因此,仅对他克莫司进行治疗药物监测(TDM)可能无法提供最佳药物水平.然而,其他影响他克莫司水平的临床因素,如血红蛋白(Hb),血细胞比容,和总胆红素(TBIL),调整他克莫司水平时应考虑。本病例报告旨在介绍临床医生及其团队考虑药代动力学预测方程,以更好地理解术后早期LT期间他克莫司剂量调整。
方法:在本案例报告中,一名18岁的泰国裔男性患者接受了原位肝移植,他克莫司被规定为基石免疫抑制剂。在术后即刻,这是肝移植中最具挑战性的时期,在这种情况下,通过考虑重要的临床因素,在临床上使用群体药代动力学预测方程来辅助他克莫司的剂量调整.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,Hb浓度的降低增加了游离药物浓度,因此增加了他克莫司的CL/F。第二,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,考虑药代动力学预测方程时,他克莫司的剂量优化将是准确的。此外,该结果可能有助于更好地了解每位移植患者术后即刻的他克莫司药代动力学变异性.
结论:血红蛋白和总胆红素是影响肝移植术后早期他克莫司口服清除率的重要临床因素。血红蛋白浓度的降低将增加游离药物浓度并因此增加他克莫司的口服清除率。总胆红素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。
BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.