Quantitative DDI victim risk assessment for nemiralisib: P450 inhibition

Cytochrome P450Fold Change in IC50aInactivation ParametersIs a DDI Risk Predicted?
KI (µM)kinact (min−1)
1A22.7No inactivation of P4501A2
2C8, 2C9, 2C19 & 2D6<1.5
  • 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.