Stepwise Regression Analysis of the Determinants of Blood Tacrolimus Concentrations in Chinese Patients with Liver Transplant

Z.      Jin; W.   x.   Zhang; B.      Chen; A.   W.   Mao; W.   M.   Cai

Abstract

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 (tacrolimusblood concentration) = 34.534 - 0.247 (age) - 0.510 (weight) + 1.688 (dose) + 6.876 (recipients CYP3A5 genotype) - 3.097 (donors CYP3A5 genotype), P < 0.01. The factors impacting patients tacrolimus blood concentrations in a descending order are weight, recipients CYP3A5 genotype, dose, age, donors CYP3A5 genotype. Among those, patients weight and recipients CYP3A5 genotype could significantly impact the blood concentration of tacrolimus. The influence of recipients CYP3A5 gene polymorphism is much more obvious than that of donors. Neither donors nor recipients MDR1 genetic polymorphisms were correlated with the blood concentration of tacrolimus.

Keywords: Liver transplantation, tacrolimus, chinese, CYP3A5, MDR1, stepwise regression analysis

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