Cytochrome P450 | Fold Change in IC50a | Inactivation Parameters | Is a DDI Risk Predicted? | |
---|---|---|---|---|
KI (µM) | kinact (min−1) | |||
1A2 | 2.7 | No inactivation of P4501A2 | ||
2B6 | 1.9 | 2.0 | 0.014 | Nob |
2C8, 2C9, 2C19 & 2D6 | <1.5 | |||
3A4 | >7.9c | 4.2 | 0.034 | Nod |
DDI, drug-drug interaction; IC50, half maximal inhibitory concentration; Ki, inactivator concentration to achieve half-maximal inactivation rate; kinact, maximal rate constant of inactivation.
↵a A less than 1.5-fold change in IC50 is deemed a low risk of DDI, and no additional inactivation data were generated.
↵b Risk discharged using static mechanistic models described by U.S. Department of Health and Human Services Food and Drug Administration (2017b) and European Medicines Agency (2012).
↵c Worst case.
↵d Risk discharged using physiologically based pharmacokinetic modeling.