Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIT15SRLZ)
  Drug Name Lorazepam Drug Info Mestranol Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antianxiety Agents Estrogens
  Structure

 Mechanism of Lorazepam-Mestranol Interaction (Severity Level: Minor)
     UGT induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Lorazepam Mestranol
      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 Lorazepam caused by Mestranol mediated induction of UGT

Recommended Action
      Management Close observation for signs and symptoms of altered benzodiazepine effect is recommended.

References
1 Abernethy DR, Greenblatt DJ, Divoll M, Arendt R, Ochs HR, Shader RI "Impairment of diazepam metabolism by low-dose estrogen-containing oral-contraceptive steroids." N Engl J Med 306 (1982): 791-2
2 Billedeau SM, Holder CL, Getek TA "High-performance liquid chromatography of the antihistamine pyrilamine and its N-oxide using electrochemical detection." J Chromatogr 534 (1990): 151-9
3 Scavone JM, Greenblatt DJ, Locniskar A, Shader RI "Alprazolam pharmacokinetics in women on low-dose oral contraceptives." J Clin Pharmacol 28 (1988): 454-7