Title : Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions.

Pub. Date : 2000

PMID : 10771452






5 Functional Relationships(s)
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1 IC50 values for the inhibition of specific probe substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, by ziprasidone, risperidone and 9-hydroxyrisperidone were also determined using human liver microsomes from three subjects. ziprasidone cytochrome P450 family 3 subfamily A member 4 Homo sapiens
2 Isoform-selective inhibitors and recombinant enzymes indicated that CYP3A4 is responsible for the formation of ziprasidone metabolites. ziprasidone cytochrome P450 family 3 subfamily A member 4 Homo sapiens
3 Similar in vitro inhibition of CYP2D6 (Ki 6.9-16 microM) and CYP3A4 (Ki 64-80 microM) was obtained with ziprasidone, risperidone and 9-hydroxyrisperidone. ziprasidone cytochrome P450 family 3 subfamily A member 4 Homo sapiens
4 The in vivo free drug concentrations associated with clinically effective doses of ziprasidone are at least 1500-fold lower than the mean Ki for either CYP2D6 inhibition or CYP3A4 inhibition. ziprasidone cytochrome P450 family 3 subfamily A member 4 Homo sapiens
5 CONCLUSIONS: Ziprasidone is predominantly metabolized by CYP3A4 in human liver microsomes and is not expected to mediate drug interactions with coadministered CYP substrates, at clinically effective doses. ziprasidone cytochrome P450 family 3 subfamily A member 4 Homo sapiens