Stepwise regression analysis of the determinants of blood tacrolimus concentrations in Chinese patients with liver transplant.

Tacrolimus (FK506) is one of the immunosuppressive drugs used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variance in pharmacokinetics make it difficult to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters may influence tacrolimus exposure. A stepwise regression analysis was used to analyze the relationship between blood concentrations of tacrolimus (54 blood samples at the day of 1 week, 2 week and one month after liver transplantation) and genetic & non-genetic factors in 18 Chinese liver transplant patients. The equation of multiple stepwise regression was: Y (tacrolimus' blood concentration) = 34.534 - 0.247 (age) - 0.510 (weight) + 1.688 (dose) + 6.876 (recipient's CYP3A5 genotype) - 3.097 (donor's CYP3A5 genotype), P < 0.01. The factors impacting patient's tacrolimus blood concentrations in a descending order are weight, recipient's CYP3A5 genotype, dose, age, donor's CYP3A5 genotype. Among those, patient's weight and recipient's CYP3A5 genotype could significantly impact the blood concentration of tacrolimus. The influence of recipient's CYP3A5 gene polymorphism is much more obvious than that of donor's. Neither donor's nor recipient's MDR1 genetic polymorphisms were correlated with the blood concentration of tacrolimus.