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US 6,673,778 B1Granted
Enzyme inhibitors for metabolic redirection
AssigneeBoard of Regents of the University of Nebraska
InventorPatrick L. Iversen
Life of this patent
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Abstract
A method is described for improving the pharmacokinetics of a drug in a subject, by co-administering oligomers, preferably PMO's (phosphorodiamidate morpholino oligonucleotides), antisense to RNAs encoding drug-metabolizing enzymes, particularly p450 enzymes. The oligomers reduce production of the drug-metabolizing enzymes, which extends drug half-life and effectiveness and/or decreases drug toxicity.
Claims15
A method of inhibiting metabolism of a drug administered to a subject, comprising
- co-administering with said drug a morpholino antisense oligomer effective to reduce expression of a cytochrome p450 enzyme that catalyzes metabolism of the drug in said subject, by hybridizing to a target RNA molecule which encodes said enzyme,
- wherein the cytochrome p450 enzyme is selected from the group consisting of CYP2B1, CYP2E1, CYP3A2, and CYP3A4,
- and wherein said morpholino antisense oligomer has a base sequence selected from the group consisting of:
- SEQ ID NO:
- 16, for inhibition of CYP2B1;
- SEQ ID NOs:
- 18-20 and 23, for inhibition of CYP2E1;
- SEQ ID NOs:
- 24 and 25, for inhibition of CYP3A2;
- and SEQ ID NOs:
- 35, 46, and 47, for inhibition of CYP3A4;
- and is administered transdermally to the subject.
9 more elements
Dependencies are inferred from the claim text.