Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDID47X0TZ)
  Drug Name Cyclosporine Drug Info Methohexital Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiviral Agents Anesthetics
  Structure

 Mechanism of Cyclosporine-Methohexital Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Cyclosporine Methohexital
      Mechanism CYP450 substrate CYP450 inducer
      Key Mechanism Factor 1
Factor Name Cytochrome P450 Structure Sequence
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, PubMed:21490593, 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). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:14559847, PubMed:12865317). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).
    Click to Show/Hide
      Mechanism Description
  • Increased metabolism of Cyclosporine caused by Methohexital mediated induction of CYP450 enzyme

Recommended Action
      Management Cyclosporine levels should be closely monitored during concomitant therapy and more frequently when a barbiturate is started or stopped. The dosage of cyclosporine should be adjusted to maintain therapeutic concentrations.

References
1 Burckart GJ, Venkataramanan R, Ptachcinski RJ "Usefulness of cyclosporin monitoring questioned." Clin Pharm 3 (1984): 243. [PMID: 6734089]
2 Carstensen H, Jacobsen N, Dieperink H "Interaction between cyclosporin A and phenobarbitone." Br J Clin Pharmacol 21 (1986): 550-1. [PMID: 3521692]
3 Cerner Multum, Inc. "Australian Product Information.".
4 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
5 Cockburn IT, Krupp P "An appraisal of drug interactions with sandimmun." Transplant Proc 21 (1989): 3845-50. [PMID: 2683269]
6 Kerr LE "Drug interactions with cyclosporine." Clin Pharm 3 (1984): 346,348. [PMID: 6467874]
7 Noguchi M, Kiuchi C, Akiyama H, et al "Interaction between cyclosporin A and anticonvulsants." Bone Marrow Transplant 9 (1992): 391. [PMID: 1617324]
8 Product Information. Neoral Soft Gelatin Capsules (cyclosporine). Sandoz Pharmaceuticals Corporation, East Hanover, NJ.
9 Product Information. Sandimmune (cyclosporine). Sandoz Pharmaceuticals Corporation, East Hanover, NJ.
10 Wideman CA "Pharmacokinetic monitoring of cyclosporine." Transplant Proc 15(1/2) (1983): 3168-75. [PMID: 1458762]
11 Yee GC, McGuire TR "Pharmacokinetic drug interactions with cyclosporin (Part I)." Clin Pharmacokinet 19 (1990): 319-32. [PMID: 2208899]