3.2 Integrating nonlinear sublingual absorption into the PBPK model
Linear regression models with logarithmically transformed dose best described the relationships between AUC- and Cmax-optimized ideal proportions and sublingual tablet and solution doses (mean R 2 = 0.756,Figure 2 ), which indicated that sublingual buprenorphine absorption is nonlinear across dose. By averaging the AUC- and Cmax-optimized linear regression models, two final absorption equations were obtained, namely, proportion of the dose sublingually absorbed equals 38.1 – 19.7 × log (Dose) and 53.3 – 25.6 × log (Dose) for sublingual tablets and solution, respectively. These equations were integrated into the PBPK model as shown in Figure 1 .