Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI0VFBECT)
Drug Name			Ritonavir		Drug Info		Thyroid, porcine		Drug Info
Drug Type		Small molecule				Hormones
Therapeutic Class		Anti-Hiv Agents				Thyroid Drugs

Mechanism of Ritonavir-Thyroid, porcine Interaction (Severity Level: Moderate)
UGT induction Click to Show/Hide Mechanism Graph

Drug Name		Ritonavir				Thyroid, porcine
Mechanism		UGT1A1 inducer				UGT1A1 substrate
Key Mechanism Factor 1
		Factor Name		UDP-glucuronosyltransferase 1A1				× Structure Sequence MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVLAPDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDSAMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLEFEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQREVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEHGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
		Gene Name		UGT1A1
		Uniprot ID		UD11_HUMAN
		KEGG Pathway		hsa:54658
		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		Increased metabolism of Thyroid, porcine caused by Ritonavir mediated induction of UGT

Recommended Action
Management		During coadministration with ritonavir, the possibility of a diminished therapeutic response to levothyroxine should be considered. Dosage adjustment as well as clinical and laboratory monitoring may be appropriate whenever ritonavir is added to or withdrawn from therapy.

References
1	Sahajpal R, Ahmed RA, Hughes CA, Foisy MM "Probable interaction between levothyroxine and ritonavir: Case report and literature review." Am J Health Syst Pharm 74 (2017): 587-592. [PMID: 28389458]
2	Touzot M, Beller CL, Touzot F, Louet AL, Piketty C "Dramatic interaction between levothyroxine and lopinavir/ritonavir in a HIV-infected patient." AIDS 20 (2006): 1210-2. [PMID: 16691080]
3	Tseng A, Fletcher D "Interaction between ritonavir and levothyroxine." AIDS 12 (1998): 2235-6. [PMID: 9833871]