Table 1.
Estimated pharmacokinetic parameters for the mPBPK model of DSTA4637A.
| Parameter (unit) | Definition | Estimates (CV %) | 95% confidence interval |
|---|---|---|---|
| σh | Vascular reflection coefficient of heart | 0.934 (0.683) | 0.922 – 0.947 |
| σl | Vascular reflection coefficient of liver | 0.957 (0.399) | 0.950 – 0.965 |
| σk | Vascular reflection coefficient of kidney | 0.964 (0.404) | 0.956 – 0.972 |
| σo | Vascular reflection coefficient of lumped tissues | 0.910 (0.804) | 0.896 – 0.924 |
| kdc (1/day) | Deconjugation rate constant | 0.141 (5.19) | 0.126 – 0.155 |
| CLp (ml/day/kg) | TAC (DAR 0 – 2) plasma proteolytic clearance | 5.26 (fixed)1 | |
| Vp,uc-dmDNA31 (ml/kg) | uc-dmDNA31 plasma volume of distribution | 1.91 × 103 (17.1) | 1.27 × 103 – 2.56 × 103 |
| Vl,uc-dmDNA31 (ml/kg) | uc-dmDNA31 liver volume of distribution | 12.8 (92.0) | 0 – 35.9 |
| Vk,uc-dmDNA31 (ml/kg) | uc-dmDNA31 kidney volume of distribution | 13.5 (43.8) | 1.86 – 25.1 |
| CLp,uc-dmDNA31 (ml/day/kg) | uc-dmDNA31 plasma clearance | 1.28 × 104 (19.6) | 7.86 × 103 – 1.77 × 104 |
| CLl,uc-dmDNA31 (ml/day/kg) | uc-dmDNA31 liver clearance | 38.9 (15.8) | 26.8 – 51.0 |
| CLk,uc-dmDNA31 (ml/day/kg) | uc-dmDNA31 kidney clearance | 18.1 (15.6) | 12.6 – 23.7 |
1Estimated CLp value did not change significantly using different analysis methods, including non-compartmental analysis, two-compartment model, and mPBPK model, and hence it was fixed to the average estimated value.