Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIGH5XFCO)
  Drug Name Pravastatin Drug Info Ritonavir Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Statins/Antihyperlipidemic Agents Anti-Hiv Agents
  Structure

 Mechanism of Pravastatin-Ritonavir Interaction (Severity Level: Moderate)
     UGT induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Pravastatin Ritonavir
      Mechanism UGT substrate UGT inducer
      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
  • Increased metabolism of Pravastatin caused by Ritonavir mediated induction of UGT

Recommended Action
      Management Pravastatin appears to be safe when coadministered with ritonavir, although the potential for diminished hypolipidemic efficacy should be considered when antiretroviral dosages of ritonavir is prescribed. Pharmacologic response to pravastatin should be monitored more closely whenever ritonavir is added to or withdrawn from therapy, and the pravastatin dosage adjusted as necessary.

References
1 Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH "Biotransformation of pravastatin sodium in humans." Drug Metab Dispos 19 (1991): 740-8. [PMID: 1680649]
2 Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. "Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047." AIDS 16 (2002): 569-577. [PMID: 11873000]
3 Product Information. Kaletra (lopinavir-ritonavir) Abbott Pharmaceutical, Abbott Park, IL.