Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI4NEZAVH)
  Drug Name Rosiglitazone Drug Info Phenobarbital Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Thiazolidinediones Anticonvulsants
  Structure

 Mechanism of Rosiglitazone-Phenobarbital Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Rosiglitazone Phenobarbital
      Mechanism CYP450 2C8 substrate CYP450 2C8 inducer
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C8
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Structure Sequence
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKVYGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRWKEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICSVVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALTRSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTETTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSDLVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFKKSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLPPSYQICFIPV
Gene Name CYP2C8
Uniprot ID CP2C8_HUMAN
KEGG Pathway hsa:1558
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). 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) (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316).
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      Mechanism Description
  • Increased metabolism of Rosiglitazone caused by Phenobarbital mediated induction of CYP450 enzyme

Recommended Action
      Management Because the antidiabetic effect of rosiglitazone is dose- and concentration-dependent, patients treated concomitantly with a CYP450 2C8 inducer may require a higher dosage of rosiglitazone. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of the CYP450 2C8 inducer, and the rosiglitazone dosage adjusted as necessary.

References
1 Baldwin SJ, Clarke SE, Chenery RJ "Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone." Br J Clin Pharmacol 48 (1999): 424-32. [PMID: 10510156]
2 Niemi M, Backman JT, Neuvonen PJ "Effects of trimethoprim and rifampin on the pharmacokinetics of the cytochrome P450 2C8 substrate rosiglitazone." Clin Pharmacol Ther 76 (2004): 239-49. [PMID: 15371985]
3 Park JY, Kim KA, Kang MH, Kim SL, Shin JG "Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects." Clin Pharmacol Ther 75 (2004): 157-62. [PMID: 15001966]
4 Product Information. Avandia (rosiglitazone) SmithKline Beecham, Philadelphia, PA.
5 Scheen AJ "Pharmacokinetic interactions with thiazolidinediones." Clin Pharmacokinet 46 (2007): 1-12. [PMID: 17201456]
6 Totah RA, Rettie AE "Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance." Clin Pharmacol Ther 77 (2005): 341-52. [PMID: 15900280]