Pharmacokinetic Evaluation of Tacrolimus in Chinese Adult Patients during the Early Stages Post-Lung Transplantation

Abstract

Background: Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. Methods: We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC0–12h). Results: Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/*3 carriers, five times higher than that in CYP3A5*3/*3 carriers (p < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC0–12h (R2 = 0.979). Conclusion: The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.

A Physiologically Based Pharmacokinetic Approach to Recommend an Individual Dose of Tacrolimus in Adult Heart Transplant Recipients

“…The pharmacokinetics of tacrolimus are complex and highly variable, especially after oral administration. The required dose to achieve similar exposures can vary between patients by over a 10-fold difference [6]. The optimal dosing strategy for rapidly achieving therapeutic concentrations remains problematic in early postoperative unfavorable clinical conditions, despite reactive adjustments to frequent tacrolimus TDM.…”