Elucidation of the biochemical basis for a clinical drug–drug interaction between atorvastatin and 5-(N-(4-((4-ethylbenzyl)thio)phenyl)sulfamoyl)-2-methyl benzoic acid (CP-778 875), a subtype selective agonist of the peroxisome proliferator-activated receptor alpha

References

• Asberg A, Hartmann A, Fjeldså E, et al. (2001). Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Am J Transplant 1:382–6
   PubMed Web of Science ®Google Scholar
• Chen C, Mireles RJ, Campbell SD, et al. (2005). Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos 33:537–46
   PubMed Web of Science ®Google Scholar
• Choi MK, Shin HJ, Choi YL, et al. (2011). Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica 41:24–34
   PubMed Web of Science ®Google Scholar
• Di L, Whitney-Pickett C, Umland JP, et al. (2011). Development of a new permeability assay using low-efflux MDCK II cells. J Pharm Sci 100:4974–85
   PubMed Web of Science ®Google Scholar
• Duval C, Müller M, Kersten S. (2007). PPAR alpha and dyslipidemia. Biochim Biophys Acta 1771:961–71
   PubMed Web of Science ®Google Scholar
• Feng B, Obach RS, Burstein AH, et al. (2008). Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro--in vivo study. Clin Pharmacol Ther 83:567–76
   PubMed Web of Science ®Google Scholar
• Feng B, Xu JJ, Bi YA, et al. (2009). Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714. Toxicol Sci 108:492–500
   PubMed Web of Science ®Google Scholar
• Frederick KS, Maurer TS, Kalgutkar AS, et al. (2009). Pharmacokinetics, disposition and lipid-modulating activity of 5-{2-[4-(3,4-difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid, a potent and subtype-selective peroxisome proliferator-activated receptor alpha agonist in preclinical species and human. Xenobiotica 39:766–81
   PubMed Web of Science ®Google Scholar
• Giri N, Agarwal S, Shaik N, et al. (2009). Substrate-dependent breast cancer resistance protein (Bcrp1/Abcg2)-mediated interactions: consideration of multiple binding sites in in vitro assay design. Drug Metab Dispos 37:560–70
   PubMed Web of Science ®Google Scholar
• Gleeson MP, Davis AM, Chohan KK, et al. (2007). Generation of in-silico cytochrome P450 1A2, 2C9, 2C19, 2D6, and 3A4 inhibition QSAR models. J Comput Aided Mol Des 21:559–73
   PubMed Web of Science ®Google Scholar
• Grube M, Köck K, Oswald S, et al. (2006). Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clin Pharmacol Ther 80:607–20
   PubMed Web of Science ®Google Scholar
• Hermann M, Asberg A, Christensen H, et al. (2004). Substantially elevated levels of atorvastatin and metabolites in cyclosporine-treated renal transplant recipients. Clin Pharmacol Ther 76:388–91
   PubMed Web of Science ®Google Scholar
• Hirano M, Maeda K, Matsushima S, et al. (2005). Involvement of BCRP (ABCG2) in the biliary excretion of pitvastatin. Mol Pharmacol 68:800–7
   PubMed Web of Science ®Google Scholar
• Holtzman CW, Wiggins BS, Spinler SA. (2006). Role of P-glycoprotein in statin drug interactions. Pharmacotherapy 26:1601–7
   PubMed Web of Science ®Google Scholar
• Hsiang B, Zhu Y, Wang Z, et al. (1999). A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem 274:37161–8
   PubMed Web of Science ®Google Scholar
• ; International Transporter ConsortiumGiacomini KM, Huang SM, Tweedie DJ, et al. (2010). Membrane transporters in drug development. Nature Rev Drug Discov 9:215–36
   PubMed Web of Science ®Google Scholar
• Jacobsen W, Kuhn B, Soldner A, et al. (2000). Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos 28:1369–78
   PubMed Web of Science ®Google Scholar
• Kalliokoski A, Niemi M. (2009). Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158:693–705
   PubMed Web of Science ®Google Scholar
• Karlgren M, Vildhede A, Norinder U, et al. (2012). Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug--drug interactions. J Med Chem 55:4740–63
   PubMed Web of Science ®Google Scholar
• Kato M, Shitara Y, Sato H, et al. (2008). The quantitative prediction of CYP-mediated drug interaction by physiologically based pharmacokinetic modeling. Pharm Res 25:1891–901
   PubMed Web of Science ®Google Scholar
• Lau YY, Okochi H, Huang Y, et al. (2006). Multiple transporters affect the disposition of atorvastatin and its two active hydroxyl metabolites: application of in vitro and ex situ systems. J Pharmacol Exp Ther 316:762–71
   PubMed Web of Science ®Google Scholar
• Lau YY, Huang Y, Frassetto L, et al. (2007). Effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. Clin Pharmacol Ther 81:194–204
   PubMed Web of Science ®Google Scholar
• Lennernäs H. (2003). Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet 42:1141–60
   PubMed Web of Science ®Google Scholar
• Li J, Volpe DA, Wang Y, et al. (2011). Use of transporter knockdown Caco-2 cells to investigate the in vitro efflux of statin drugs. Drug Metab Dispos 39:1196–202
   PubMed Web of Science ®Google Scholar
• Maeda K, Ikeda Y, Fujita T, et al. (2011). Identification of the rate-determining process in the hepatic clearance of atorvastatin in a clinical cassette microdosing study. Clin Pharmacol Ther 90:575–81
   PubMed Web of Science ®Google Scholar
• Neuvonen PJ, Niemi M, Backman JT. (2006). Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 80:565–81
   PubMed Web of Science ®Google Scholar
• Niessen J, Jedlitschky G, Grube M, et al. (2009). Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos 37:1129–37
   PubMed Web of Science ®Google Scholar
• Pettersen JC, Pruimboom-Brees I, Francone OL, et al. (2012). The PPARα agonists fenofibrate and CP-778875 cause increased β-oxidation, leading to oxidative injury in skeletal and cardiac muscle in the rat. Toxicol Pathol 40:435–47
   PubMed Web of Science ®Google Scholar
• Shah A, Radar DJ, Millar JS. (2010). The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. Atherosclerosis 210:35–40
   PubMed Web of Science ®Google Scholar
• Tenenbaum A, Fisman EZ. (2012). Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction. Cardiovasc Diabetol 11:125. doi: 10.1186/1475-2840-11-125
   PubMed Web of Science ®Google Scholar
• Varma MV, Chang G, Lai Y, et al. (2012a). Physicochemical property space of hepatobiliary transport and computational models for predicting rat biliary excretion. Drug Metab Dispos 40:1527–37
   PubMed Web of Science ®Google Scholar
• Varma MV, Lai Y, Feng B, et al. (2012b). Physiologically based modeling of pravastatin transporter-mediated hepatobiliary disposition and drug--drug interactions. Pharm Res 29:2860–73
   PubMed Web of Science ®Google Scholar
• Walsky RL, Obach RS. (2004). Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647–60
   PubMed Web of Science ®Google Scholar
• Yao M, Zhang H, Chong S, et al. (2003). A rapid and sensitive LC/MS/MS assay for quantitative determination of digoxin in rat plasma. J Pharm Biomed Anal 32:1189–97
   PubMed Web of Science ®Google Scholar
• Yang SH, Choi JS, Choi DH. (2011). Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of losartan and its main metabolite EXP-3174 in rats: possible role of CYP3A4 and P-gp inhibition by HMG-CoA reductase inhibitors. Pharmacology 88:1–9
   PubMed Web of Science ®Google Scholar