Clinical monitoring method of area under the concentrations-time curve after the first oral tacrolimus

Abstract

Objective To assess the predictability of individual tacrolimus (FK506) concentrations at different time points for the area under the curve (AUC) and to find the best sampling time for the abbreviated AUC to predict the total body exposure of tacrolimus. Methods 16 primary kidney transplant recipients were treated with methylprednisolone and antilymphocyte globulin for 3 days. The first tacrolimus oral dose, 0.075 mg/kg, was given at day 3 after transplantation. Blood samples were obtained at 0.5,1.0, 1.5, 2.0, 3.0, 5.0, 8.0, and 12.0 hours since taking the first oral dose. The tacrolimus blood concentration was measured by ELISA. Twelve-hour AUC (AUC12) for each patient was calculated using linear trapezoid rule. Associations between blood concentration at each sampling time points and the AUC12were measured by Pearson correlation coefficients. Abbreviated sampling equations were derived by multiple,stepwise regression analyses performed using AUC12 as the dependent variables. The variance in the strength of association between predicted AUC (AUCp) and AUC12 was reflected by the linear regression coefficient the minimum AUC12. The correlation between all the time points concentration, except C1.0, all the drug concentrations at different time points were significantly correlated with AUC ( all P＜0.05 ). Stepwise multiple regression showed that C5.0 might be the best predictor of the total body exposure of tacrolimus (R=0.92, R2=0.85). According to an abbreviated AUC monitoring strategy, the concentrations at hours 5 and 1.5 or hours 5, 1.5, and 3 were well correlated with AUC (R=0.97, R2=0.94 and R=0.99, R2=0.99, respectively). Conclusion Tacrolimus AUC12 shows remarkable interindividual variation after the first oral dose in Chinese renal transplant recipients. C5 may be the best predictor of the first AUC12. Twopoint sampling method using C5 and C1.5 and the three-point sampling method using C5, C1.5, and C3 may be the best abbreviated AUC to cost-effective tacrolimus monitoring strategy. Key words: Kidney transplantation; Tacrolimus ; Pharmacokinetics