TABLE 2

Quantitative DDI victim risk assessment for nemiralisib: P450 inhibition

Cytochrome P450	Fold Change in IC₅₀^{^a}	Inactivation Parameters		Is a DDI Risk Predicted?
Cytochrome P450	Fold Change in IC₅₀^{^a}	K_I (µM)	k_inact (min⁻¹)	Is a DDI Risk Predicted?
1A2	2.7	No inactivation of P4501A2
2B6	1.9	2.0	0.014	No^{^b}
2C8, 2C9, 2C19 & 2D6	<1.5
3A4	>7.9^{^c}	4.2	0.034	No^{^d}

DDI, drug-drug interaction; IC₅₀, half maximal inhibitory concentration; K_i, inactivator concentration to achieve half-maximal inactivation rate; k_inact, 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.