General Information of Drug Combination (ID: DC38281)

Drug Combination Name
AKB-6548 Pravastatin
Indication
Disease Entry Status REF
Drug Interaction Potentiation Phase 1 [1]
Component Drugs AKB-6548   DM2EJM3 Pravastatin   DM6A0X7
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AKB-6548
Disease Entry ICD 11 Status REF
Anaemia 3A90 Phase 3 [2]
AKB-6548 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HIF-prolyl hydroxylase (HPH) TTJQFBG NOUNIPROTAC Modulator [5]
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Indication(s) of Pravastatin
Disease Entry ICD 11 Status REF
Adult acute monocytic leukemia N.A. Approved [3]
Arteriosclerosis BD40 Approved [3]
Hypercholesterolaemia 5C80.0 Approved [4]
Hyperlipidemia, familial combined, LPL related N.A. Approved [3]
Hypertriglyceridemia 5C80.1 Approved [3]
Stroke 8B20 Investigative [3]
Pravastatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [6]
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Pravastatin Interacts with 11 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [10]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [11]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [12]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [14]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [15]
Probable small intestine urate exporter (SLC17A4) DTHE530 S17A4_HUMAN Substrate [16]
Organic anion transporter 7 (SLC22A9) DTDI5S3 S22A9_HUMAN Substrate [17]
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⏷ Show the Full List of 11 DTP(s)
Pravastatin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [18]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [19]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [20]
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Pravastatin Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Increases ADR [21]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Increases ADR [21]
Kinesin-like protein KIF6 (KIF6) OTDH3MR4 KIF6_HUMAN Increases ADR [22]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases ADR [21]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases ADR [23]
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References

1 ClinicalTrials.gov (NCT03801733) Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
2 ClinicalTrials.gov (NCT03242967) Study to Evaluate Three Times Per Week (TIW) Oral Dosing of Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (TRILOGY). U.S. National Institutes of Health.
3 Pravastatin FDA Label
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2953).
5 DOI: 10.1038/nrd4422
6 A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9.
7 Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney. J Control Release. 2002 Jan 17;78(1-3):43-54.
8 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
9 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
10 The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
11 Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther. 2005 Aug;314(2):876-82.
12 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
13 Inhibition of human organic anion transporter 3 mediated pravastatin transport by gemfibrozil and the metabolites in humans. Xenobiotica. 2007 Apr;37(4):416-26.
14 Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
15 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
16 A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter. Am J Physiol Cell Physiol. 2012 Jun 1;302(11):C1652-60.
17 Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors. Pharmacogenomics J. 2016 Aug;16(4):341-51.
18 Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Clin Pharmacokinet. 2000 Dec;39(6):397-412.
19 Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999 Feb;27(2):173-9.
20 In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996;50(3):209-15.
21 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
22 Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol. 2008 Jan 29;51(4):435-43. doi: 10.1016/j.jacc.2007.05.057.
23 Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004 Jun 16;291(23):2821-7. doi: 10.1001/jama.291.23.2821.