On average for tablet and solution formulations, the geometric mean (95% CI) AUC, CL/F, Cmax, and Tmax P/O ratios were 0.99 (0.86–1.12), 1.04 (0.92–1.18), 1.24 (1.09–1.40), and 1.07 (0.95–1.20), respectively. All predicted vs. observed buprenorphine concentration-time profiles following sublingual administration are shown in Figure 4. Predicted vs. observed goodness-of-fit plots for AUC, CL/F, and Tmax did not reveal a bias, as data points were symmetrically distributed across the line of equality (Figure 5). Similarly, dose vs. P/O ratio goodness-of-fit plots suggested an unbiased prediction of AUC, CL/F, and Tmax across dose (Figure 6), although clinical studies in which participants received sublingual solution were relatively few and the dose range was smaller. Although goodness-of-fit plots indicated a modest trend towards overpredicting Cmax, especially for high doses, the PBPK model’s predictive performance of buprenorphine PK following sublingual administration seemed to overall be adequate for both formulations across a wide dose range in healthy volunteers.