Certara Investor Day Presentation Deck
Ibrutinib model used to inform dose adjustments in label
"The simulations of PBPK model provided a dose optimization strategy for combined use
of ibrutinib with specific CYP3A inhibitors or inducers."
- from the FDA label report, June 28, 2013
CYP3A
modulators
Inhibitors
Inducers
Goal
Simulated ibrutinib exposure
vs. that of 560 mg without
inhibitor should be <2 fold
Simulated ibrutinib exposure
vs. that of 140 mg without
inducer should be >1
CYP3A interaction
mechanisms of co-
medications
Strong, reversible, minimal
accumulation (e.g. ketoconazole)
Strong, time-dependent (e.g.
ritonavir)
Moderate
Moderate
Strong
Ibrutinib dosing
Reduce to 140 mg and give 2
hours before inhibitor
Do not use
Reduce to140 mg
No dose adjustment
Do not use
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