Pharmacokinetic Evaluation of Tacrolimus in Chinese Adult Patients Receiving Voriconazole During the Early Stage Post-Lung Transplantation

Abstract

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 its pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. We enrolled 14 lung transplant recipients who were treated with tacrolimus and voriconazole. We then collected intensive blood samples within a 12-hour dosing interval and analysed them via liquid chromatography-mass spectrometry. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of physio-pathological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we then investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the curve (AUC0 − 12h). Our results showed a mean apparent clearance (CL/F) rate of 14.2 ± 11.0 L/h, with CYP3A5*1 carriers having a CL/F rate five times higher than non-carriers (P < 0.001). Furthermore, tacrolimus concentration 4 h after the administration had the strongest correlation with AUC0 − 12h (R2 = 0.979). In summary, tacrolimus pharmacokinetics varied largely between patients during the early-stage post-lung transplantation, which could be partly explained by CYP3A5 genetic polymorphisms. Therefore, it is crucial to closely monitor tacrolimus blood concentration in the early stages after lung transplantation.