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 R2 = 0.756, Figure 3), 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.