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: