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

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 CYP3A53 and CYP3A41G 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 (AUC).

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 CYP3A53/*3 carriers ( < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC (R = 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.