3.1 Validation of the PBPK model’s predictive performance
following intravenous administration
The structure of the full PBPK model was first externally validated by
determining P/O ratios of AUC0–∞, CL, and
Cmax following intravenous administration of
buprenorphine in healthy volunteers. Twelve PK studies, spanning a dose
range of 0.3–16 mg and including a total of 69 subjects (aged 20 to
66.8 years) with 89 concentration-time profiles, were used for
intravenous model validation (Table
2 ).41,47-51 For all 12 PK studies, the P/O ratios of
AUC0–∞, CL, and Cmax, fell within the
2-fold prediction error range. Geometric mean (95% CI)
AUC0–∞, CL, and Cmax P/O ratios were
1.01 (0.90–1.13), 0.95 (0.84–1.08), and 0.91 (0.78–1.05),
respectively, indicating adequate predictive performance of these PK
parameters following intravenous administration across a wide dose range
in healthy volunteers. All predicted vs . observed buprenorphine
concentration-time profiles following intravenous administration are
shown in Supplementary Figure 1 .