Then, AUC values were calculated according to the new recommended doses. Variabilities of AUC were shown by the range between minimum and maximum values and the coefficient of variation (CV). The rate of achieving the targeted AUC window (900-1350 μM·min) was also listed.
2.6 Optimized Sampling Scheme
The final PPK model provides information on typical PK parameters and variabilities associated with these values as well as how specific covariates (e.g. BSA, AST, genotypes) influence the PK of BU. After evaluating final model predictive performance, filtrating optimal LSS was considered to optimize the sampling scheme for TDM. Candidate sampling points included: (1) 2, 2.25, 4 and 6 hours; (2) 2, 2.5, 4 and 6 hours; (3) 2.25, 2.5, 4 and 6 hours; (4) 2, 4 and 6 hours; (5) 2.25, 4 and 6 hours; (6) 2.5, 4 and 6 hours; (7) 2, 2.25 and 4 hours; (8) 2, 2.25 and 6 hours; (9) 2, 2.5 and 4 hours; (10) 2, 2.5 and 6 hours; (11) 2.25, 2.5 and 4 hours; (12) 2.25, 2.5 and 6 hours; (13) 2 and 4 hours; (14) 2 and 6 hours; (15) 2.25 and 4 hours; (16) 2.25 and 6 hours; (17) 2.5 and 4 hours; (18) 2.5 and 6 hours after the beginning of first infusion. The blood drug concentration at 2.25 hours after administration was simulated by the final model. Each candidate LSS was tested by Bayesian method to obtain AUC0-6h of each patient. APE, MAPE and rRMSE were calculated by comparing the predicted AUC0-6hderived from the LSS with the actual AUC0-6h obtained from each patient’s full concentration-time samples, as according toEquation 2, 3 and 4 to evaluate predictive accuracy: