Validation and evaluation of the PBPK model’s predictive performance following sublingual administration
The PBPK model with the developed description of nonlinear sublingual buprenorphine absorption was subsequently externally validated by determining P/O ratios of AUC, CL/F, Cmax, and Tmax following sublingual administration of buprenorphine tablets and solution separately. For validation of the PBPK model’s predictive performance following sublingually administered tablets, 16 PK studies, spanning a dose range of 2–32 mg and including a total of 296 subjects (aged 19 to 54) with 419 concentration-time profiles, were used (Table 3) [25, 27, 29, 52-54]. For all 16 PK studies, the P/O ratios of AUC, CL/F, Cmax, and Tmax fell within the 2-fold prediction error range. Geometric mean (95% CI) AUC, CL/F, Cmax, and Tmax P/O ratios were 0.96 (0.82–1.12), 1.07 (0.92–1.24), 1.20 (1.05–1.37), and 1.07 (0.94–1.23), respectively.