Details of Drug-Drug Interaction
| Drug General Information (ID: DDI98PF04M) | |||||||||
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| Drug Name | Mifepristone | Drug Info | Pioglitazone | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Uterotonic Agents | Antidiabetic Agents | |||||||
| Structure | |||||||||
| Mechanism of Mifepristone-Pioglitazone Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Mifepristone | Pioglitazone | |||||||
| Mechanism | CYP450 2C8 inhibitor | CYP450 2C8 substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2C8 |
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Structure
Sequence
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKVYGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRWKEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICSVVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALTRSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTETTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSDLVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFKKSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLPPSYQICFIPV
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| Gene Name | CYP2C8 | ||||||||
| Uniprot ID | CP2C8_HUMAN | ||||||||
| KEGG Pathway | hsa:1558 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Caution is advised if mifepristone must be used concomitantly with medications that are substrates of CYP450 2C8 and/or 2C9, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever mifepristone is added to or withdrawn from therapy. The lowest dosage of sensitive substrates (e.g., repaglinide, warfarin) should be used whenever possible. Because mifepristone is eliminated slowly from the body, drug interactions may be observed for a prolonged period following discontinuation (approximately 2 to 3 weeks if mifepristone had been administered chronically to steady state). | ||||||||
| References | |||||||||||||||||||
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| 1 | Product Information. Korlym (mifepristone). Corcept Therapeutics Incorporated, Menlo Park, CA. | ||||||||||||||||||