Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIWQUDZ4S)
Drug Name			Propofol		Drug Info		Olaparib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anxiolytics/Sedatives/Hypnotics				Poly (Adp-Ribose) Polymerase Inhibitors
Structure

Mechanism of Propofol-Olaparib Interaction (Severity Level: Moderate)
CYP450 enzyme induction Click to Show/Hide Mechanism Graph

Drug Name		Propofol				Olaparib
Mechanism		CYP450 2C9 substrate				CYP450 2C9 inducer
Key Mechanism Factor 1
		Factor Name		Cytochrome P450 2C9				× Structure Sequence MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV
		Gene Name		CYP2C9
		Uniprot ID		CP2C9_HUMAN
		KEGG Pathway		hsa:1559
		Protein Family		Cytochrome P450 family
		Protein Function		A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). 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:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031). Click to Show/Hide
Mechanism Description		Increased metabolism of Propofol caused by Olaparib mediated induction of CYP450 enzyme

Recommended Action
Management		Caution is advised if olaparib is used concomitantly with drugs that are substrates of CYP450 1A2 and/or 2B6. Pharmacologic response and serum levels should be monitored more closely whenever olaparib is added to or withdrawn from therapy with these drugs. Dosage adjustments may be required if an interaction is suspected.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".