Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDITS1XAGK)
  Drug Name Rifabutin Drug Info Fludrocortisone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antibiotics Antiinflammatory Agents
  Structure

 Mechanism of Rifabutin-Fludrocortisone Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Rifabutin Fludrocortisone
      Mechanism CYP450 inducer CYP450 substrate
      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 Fludrocortisone caused by Rifabutin mediated induction of CYP450 enzyme

Recommended Action
      Management Patients should be monitored for altered corticosteroid effects. Dosage increases may be necessary. Two- to threefold increases in prednisolone dosage have been recommended.

References
1 Bergrem H, Refvem OK "Altered prednisolone pharmacokinetics in patients treated with rifampicin." Acta Med Scand 213 (1983): 339-43. [PMID: 6880856]
2 Kyriazopoulou V, Parparousi O, Vagenakis AG "Rifampicin-induced adrenal crisis in Addisonian patients receiving corticosteroid replacement therapy." J Clin Endocrinol Metab 59 (1984): 1204-6. [PMID: 6490796]
3 Lee KH, Shin JG, Chong WS, Kim S, Lee JS, Jang IJ, Shin SG "Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin." Eur J Clin Pharmacol 45 (1993): 287-9. [PMID: 8276057]
4 McAllister WA, Thompson PJ, Al-Habet SM, Rogers HJ "Rifampicin reduces effectiveness and bioavailability of prednisolone." Br Med J 286 (1983): 923-5. [PMID: 6403136]
5 Powell-Jackson PR, Gray BJ, Heaton RW, et al "Adverse effect of rifampicin administration on steroid-dependent asthma." Am Rev Respir Dis 128 (1983): 307-10. [PMID: 6349444]
6 Strayhorn VA, Baciewicz AM, Self TH "Update on rifampin drug interactions, III." Arch Intern Med 157 (1997): 2453-8. [PMID: 9385296]
7 Venkatesan K "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet 22 (1992): 47-65. [PMID: 1559307]