Title : Accelerating Clinical Development of Idasanutlin through a Physiologically Based Pharmacokinetic Modeling Risk Assessment for CYP450 Isoenzyme-Related Drug-Drug Interactions.

Pub. Date : 2022 Mar

PMID : 34937801






3 Functional Relationships(s)
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Compound Name
Protein Name
Organism
1 Idasanutlin"s clearance is dependent on CYP3A4/2C8, forming its major circulating metabolite M4, with contributions from UGT1A3 and biliary excretion. RG7388 cytochrome P450 family 3 subfamily A member 4 Homo sapiens
2 Idasanutlin and M4 have low permeability, very low clearance and extremely low unbound fraction in plasma (<0.001) which makes in vitro data showing inhibition on CYP3A4/2C8 enzymes challenging to translate to clinical relevance. RG7388 cytochrome P450 family 3 subfamily A member 4 Homo sapiens
3 Co-administered strong CYP3A and CYP2C8 inhibitors might lead to weak or moderate idasanutlin exposure increases and the strong inducer rifampicin might cause moderate exposure reduction. RG7388 cytochrome P450 family 3 subfamily A member 4 Homo sapiens