Parameter inputs used in victim mechanistic static mathematical model predictions of dabrafenib DDIs
| Parameter Input | Values | ||
|---|---|---|---|
| P | 148 nm/sc | ||
| Qvilli | 18 l/ha | ||
| A | 6,600 cm2a | ||
| CYP3A4g | 66.2 nmoles/total gutb | ||
| CYP3A4h | 142 pmole/mg mp2b | ||
| Microsomal yield | 29.3b | ||
| Peff, man | 0.44 e-4cm/sn | ||
| HLM CLint3A4 | 6.1 ul/min/ mg proteinc | ||
| fmCYP3A4 | 0.24c | ||
| fmCYP2C8 | 0.67c | ||
| Kdeg,g | 0.000502 kdeg/minm | ||
| Ketoconazole | Gemfibrozil | Gemfibrozil-1-Ο−β-Glucuronide | |
| Ki | 0.02 μMd | 9.3h | 10.1k |
| Kinact | NA | NA | 0.21k |
| KI | NA | NA | 10.1h |
| fu | 0.01e | 0.03i | 0.115l |
| Cmax (μM) | 13.17f | 102j | 56l |
| Dose (mg) | 400 | 600 | NA |
| Liver:plasma | 2b | 2b | 2b |
| Ka (min−1) | 0.036e | 0.05i | NA |
| Fa | 1 | ||
| Qh | 1,617 ml/ming | ||
| Fa | 1 | ||
| Fg | 0.85 | 1 | NA |
| Qg | 300 ml/ming | ||
↵a Yang et al., 2007b; bRodgers et al., 2005a, 2005b; Rodgers and Rowland, 2006, 2007; cIn vitro data measured separately; dUniversity of Washington Database; ewww.drugbank.ca; fRxList.com; gU.S. Food and Drug Administration, 2012; hVandenBrink et al., 2011; iVarma et al., 2012; jSchneck et al., 2004; kOgilvie et al., 2006; lHonkalammi et al., 2011; mYang et al., 2008; nIn Silico, Simcyp Ltd v8.20, Sheffield, UK.