Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIIVT7U1A)
Drug Name			Zidovudine		Drug Info		Ethinylestradiol		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anti-Hiv Agents				Estrogens
Structure

Mechanism of Zidovudine-Ethinylestradiol Interaction (Severity Level: Minor)
UGT inhibition Click to Show/Hide Mechanism Graph

Drug Name		Zidovudine				Ethinylestradiol
Mechanism		UGT substrate				UGT inhibitor
Key Mechanism Factor 1
		Factor Name		UDP-glucuronosyltransferase				Structure Sequence
		Protein Family		UDP-glycosyltransferase family
		Protein Function		[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558). Click to Show/Hide
Mechanism Description		Decreased metabolism of Zidovudine caused by Ethinylestradiol mediated inhibition of UGT

References
1	Lotterer E, Ruhnke M, Trautman M, et al "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol 40 (1991): 305-8. [PMID: 2060570]
2	Sim SM, Back DJ, Breckenridge AM "The effect of various drugs on the glucuronidation of zidovudine (azidothymidine AZT) by human liver microsomes." Br J Clin Pharmacol 32 (1991): 17-21. [PMID: 1909542]
3	Unadkat JD, Collier AC, Crosby SS, et al "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS 4 (1990): 229-32. [PMID: 2350441]