Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMBY31K)

• Drug Name: Rivoglitazone Drug Info
• Synonyms: CS-011; DE-101; Rivoglitazone (ophthalmic); Rivoglitazone (ophthalmic), Santen; CS-011 (ophthalmic), Santen

Indication

Disease Entry	ICD 11	Status	REF
Ocular inflammation	9C61.24	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 3055168
  CAS Number: CAS 185428-18-6
  TTD Drug ID: DMBY31K
  INTEDE Drug ID: DR1432

Molecule-Related Drug Atlas

Drug(s) Targeting Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[5]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[6]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[7]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[8]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[6]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[9]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[10]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[11]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[12]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[25]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[27]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[28]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[24]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[29]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[30]

Drug(s) Metabolized By UDP-glucuronosyltransferase 2B7 (UGT2B7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[31]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[32]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[33]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[29]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[22]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[34]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[35]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[36]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[37]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A3 (UGT1A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[38]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[39]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[22]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[40]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[41]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[34]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[35]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[42]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[37]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Agonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[4]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Substrate	[4]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Substrate	[4]

References

• [1] ClinicalTrials.gov (NCT00571519) Randomized, Double-blind, Active-controlled, Study of Rivoglitazone in Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
• [2] A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes. Diabetes Obes Metab. 2011 Sep;13(9):806-13.
• [3] Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14.
• [4] In vitro metabolism of rivoglitazone, a novel peroxisome proliferator-activated receptor gama agonist, in rat, monkey, and human liver microsomes and freshly isolated hepatocytes. Drug Metab Dispos. 2011 Jul;39(7):1311-9.
• [5] Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer. 2003 May 1;104(5):597-602.
• [6] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [7] Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-gamma agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467-74.
• [8] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [9] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [10] Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with... Clin Ther. 2005 Aug;27(8):1181-95.
• [11] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [12] Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J Clin Pharmacol. 2003 Nov;43(11):1244-56.
• [13] Determination of chiglitazar, a dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist, in human plasma by liquid chromatograph... Pharmazie. 2007 Nov;62(11):825-9.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [19] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [22] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [23] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [24] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [25] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [26] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [27] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [28] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [29] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [30] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [31] Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
• [32] Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultra-performance liquid chromatography with MS detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):84-90.
• [33] Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
• [34] Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
• [35] Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
• [36] Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
• [37] Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
• [38] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
• [39] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [40] UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7.
• [41] Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
• [42] Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8.