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Review Article

Evaluation of pregnane X receptor (PXR)-mediated CYP3A4 drug-drug interactions in drug development

Pages 3-14 | Received 14 Sep 2012, Accepted 12 Oct 2012, Published online: 21 Jan 2013

References

  • Ai, N., Krasowski, M. D., Welsh, W. J., Ekins, S. (2009). Understanding nuclear receptors using computational methods. Drug Discov Today 14:486–494.
  • Bertilsson, G., Heidrich, J., Svensson, K., Asman, M., Jendeberg, L., Sydow-Backman, M., et al. (1998). Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci U S A 95:12208–12213.
  • Bertilsson, L., Hojer, B., Tybring, G., Osterloh, J., Rane, A. (1980). Autoinduction of carbamazepine metabolism in children examined by a stable isotope technique. Clin Pharmacol Ther 27:83–88.
  • Blumberg, B., Evans, R. M. (1998). Orphan nuclear receptors—new ligands and new possibilities. Genes Dev 12:3149–3155.
  • Carnahan, V. E., Redinbo, M. R. (2005). Structure and function of the human nuclear xenobiotic receptor PXR. Curr Drug Metab 6:357–367.
  • Chu, V., Einolf, H. J., Evers, R., Kumar, G., Moore, D., Ripp, S., et al. (2009). In vitro and in vivo induction of cytochrome p450: a survey of the current practices and recommendations: a pharmaceutical research and manufacturers of america perspective. Drug Metab Dispos 37:1339–1354.
  • Cui, X., Thomas, A., Gerlach, V., White, R. E., Morrison, R. A., Cheng, K. C. (2008). Application and interpretation of hPXR screening data: validation of reporter signal requirements for prediction of clinically relevant CYP3A4 inducers. Biochem Pharmacol 76:680–689.
  • Ekins, S., Chang, C., Mani, S., Krasowski, M. D., Reschly, E. J., Iyer, M., et al. (2007). Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites. Mol Pharmacol 72:592–603.
  • El-Sankary, W., Gibson, G. G., Ayrton, A., Plant, N. (2001). Use of a reporter gene assay to predict and rank the potency and efficacy of CYP3A4 inducers. Drug Metab Dispos 29:1499–1504.
  • EMA. (2012). Guideline on the investigation of drug interactions. Guideline on the investigation of drug interactions. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf. Accessed on September XX, 2012.
  • Enoru-Eta, J., Yengi, L. G., He, X., Kubik, J., Kao, J., Scatina, J. (2010). Development of a UGT1A1 reporter gene assay for induction studies: correlation between reporter gene data and regulation of UGT1A1 in human hepatocytes. Drug Metab Lett 4:31–38.
  • Fahmi, O. A., Ripp, S. L. (2010). Evaluation of models for predicting drug-drug interactions due to induction. Expert Opin Drug Metab Toxicol 6:1399–1416.
  • FDA. (2012). Guidance for industry: drug interaction studies-study design, data analysis,implications for dosing, and labeling recommendations. Guidance for industry: drug interaction studies-study design, data analysis,implications for dosing, and labeling recommendations. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf.
  • Fotsch, C., Bartberger, M. D., Bercot, E. A., Chen, M., Cupples, R., Emery, M., et al. (2008). Further studies with the 2-amino-1,3-thiazol-4(5H)-one class of 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: reducing pregnane X receptor activity and exploring activity in a monkey pharmacodynamic model. J Med Chem 51:7953–7967.
  • Gao, Y. D., Olson, S. H., Balkovec, J. M., Zhu, Y., Royo, I., Yabut, J., et al. (2007). Attenuating pregnane X receptor (PXR) activation: a molecular modelling approach. Xenobiotica 37:124–138.
  • Gonzalez, F. J., Yu, A. M. (2006). Cytochrome P450 and xenobiotic receptor humanized mice. Annu Rev Pharmacol Toxicol 46:41–64.
  • Hariparsad, N., Carr, B. A., Evers, R., Chu, X. (2008). Comparison of immortalized Fa2N-4 cells and human hepatocytes as in vitro models for cytochrome P450 induction. Drug Metab Dispos 36:1046–1055.
  • Harper, S., Avolio, S., Pacini, B., Di Filippo, M., Altamura, S., Tomei, L., et al. (2005). Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase. J Med Chem 48:4547–4557.
  • Hasegawa, M., Kapelyukh, Y., Tahara, H., Seibler, J., Rode, A., Krueger, S., et al. (2011). Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line. Mol Pharmacol 80:518–528.
  • Hewitt, N. J., De Kanter, R., Lecluyse, E. (2007). Induction of drug metabolizing enzymes: a survey of in vitro methodologies and interpretations used in the pharmaceutical industry—do they comply with FDA recommendations? Chem Biol Interact 168:51–65.
  • Jeong, H., Choi, S., Song, J. W., Chen, H., Fischer, J. H. (2008). Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica 38:62–75.
  • Jones, S. A., Moore, L. B., Shenk, J. L., Wisely, G. B., Hamilton, G. A., Mckee, D. D., et al. (2000). The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27–39.
  • Khandelwal, A., Krasowski, M. D., Reschly, E. J., Sinz, M. W., Swaan, P. W., Ekins, S. (2008). Machine learning methods and docking for predicting human pregnane X receptor activation. Chem Res Toxicol 21:1457–1467.
  • Kim, S., Dinchuk, J. E., Anthony, M. N., Orcutt, T., Zoeckler, M. E., Sauer, M. B., et al. (2010). Evaluation of cynomolgus monkey pregnane X receptor, primary hepatocyte, and in vivo pharmacokinetic changes in predicting human CYP3A4 induction. Drug Metab Dispos 38:16–24.
  • Kim, S., Pray, D., Zheng, M., Morgan, D. G., Pizzano, J. G., Zoeckler, M. E., et al. (2008). Quantitative relationship between rifampicin exposure and induction of Cyp3a11 in SXR humanized mice: extrapolation to human CYP3A4 induction potential. Drug Metab Lett 2:169–175.
  • Kliewer, S. A., Goodwin, B., Willson, T. M. (2002). The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 23:687–702.
  • Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., et al. (1998). An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92:73–82.
  • Lemaire, G., Benod, C., Nahoum, V., Pillon, A., Boussioux, A. M., Guichou, J. F., et al. (2007). Discovery of a highly active ligand of human pregnane x receptor: a case study from pharmacophore modeling and virtual screening to “in vivo” biological activity. Mol Pharmacol 72:572–581.
  • Li, L., Sinz, M. W., Zimmermann, K., Wang, H. (2012). An insulin-like growth factor 1 receptor inhibitor induces CYP3A4 expression through a pregnane X receptor-independent, noncanonical constitutive androstane receptor-related mechanism. J Pharmacol Exp Ther 340:688–697.
  • Matter, H., Anger, L. T., Giegerich, C., Gussregen, S., Hessler, G., Baringhaus, K. H. (2012). Development of in silico filters to predict activation of the pregnane X receptor (PXR) by structurally diverse drug-like molecules. Bioorg Med Chem 20:5352–5365.
  • Mcginnity, D. F., Zhang, G., Kenny, J. R., Hamilton, G. A., Otmani, S., Stams, K. R., et al. (2009). Evaluation of multiple in vitro systems for assessment of CYP3A4 induction in drug discovery: human hepatocytes, pregnane X receptor reporter gene, and Fa2N-4 and HepaRG cells. Drug Metab Dispos 37:1259–1268.
  • Nishimura, M., Koeda, A., Suganuma, Y., Suzuki, E., Shimizu, T., Nakayama, M., et al. (2007). Comparison of inducibility of CYP1A and CYP3A mRNAs by prototypical inducers in primary cultures of human, cynomolgus monkey, and rat hepatocytes. Drug Metab Pharmacokinet 22:178–186.
  • Park, J. Y., Kim, K. A., Kang, M. H., Kim, S. L., Shin, J. G. (2004). Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects. Clin Pharmacol Ther 75:157–162.
  • Prueksaritanont, T., Kuo, Y., Tang, C., Li, C., Qiu, Y., Lu, B., et al. (2006). In vitro and in vivo CYP3A64 induction and inhibition studies in rhesus monkeys: a preclinical approach for CYP3A-mediated drug interaction studies. Drug Metab Dispos 34:1546–1555.
  • Raucy, J. L., Lasker, J. M. (2010). Current in vitro high throughput screening approaches to assess nuclear receptor activation. Curr Drug Metab 11:806–814.
  • Rew, Y., McMinn, D. L., Wang, Z., He, X., Hungate, R. W., Jaen, J. C., et al. (2009). Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors. Bioorg Med Chem Lett 19:1797–1801.
  • Schlegel, K. A., Yang, Z. Q., Reger, T. S., Shu, Y., Cube, R., Rittle, K. E., et al. (2010). Discovery and expanded SAR of 4,4-disubstituted quinazolin-2-ones as potent T-type calcium channel antagonists. Bioorg Med Chem Lett 20:5147–5152.
  • Simonsson, U. S., Jansson, B., Hai, T. N., Huong, D. X., Tybring, G., Ashton, M. (2003). Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9. Clin Pharmacol Ther 74:32–43.
  • Sinz, M., Kim, S. (2006). Stem cells, immortalized cells, and primary cells in ADMET assays. Drug Discov Today Technol 3:79–85.
  • Sinz, M., Kim, S., Zhu, Z., Chen, T., Anthony, M., Dickinson, K., Rodrigues, A. D. (2006). Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known CYP3A4 drug interactions. Curr Drug Metab 7:375–388.
  • Sinz, M., Wallace, G., Sahi, J. (2008). Current industrial practices in assessing CYP450 enzyme induction: preclinical and clinical. AAPS J 10:391–400.
  • Tolson, A. H., Wang, H. (2010). Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR. Adv Drug Deliv Rev 62:1238–1249.
  • Watkins, R. E., Maglich, J. M., Moore, L. B., Wisely, G. B., Noble, S. M., Davis-Searles, P. R., et al. (2003). 2.1 A crystal structure of human PXR in complex with the St. John’s wort compound hyperforin. Biochemistry 42:1430–1438.
  • Watkins, R. E., Wisely, G. B., Moore, L. B., Collins, J. L., Lambert, M. H., Williams, S. P., et al. (2001). The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 292:2329–2333.
  • Wipf, P., Gong, H., Janjic, J. M., Li, S., Day, B. W., Xie, W. (2007). New opportunities for pregnane X receptor (PXR) targeting in drug development. Lessons from Enantio- and species-specific PXR ligands identified from a discovery library of amino acid analogues. Mini Rev Med Chem 7:617–625.
  • Worboys, P. D., Carlile, D. J. (2001). Implications and consequences of enzyme induction on preclinical and clinical drug development. Xenobiotica 31:539–556.
  • Xue, Y., Moore, L. B., Orans, J., Peng, L., Bencharit, S., Kliewer, S. A., et al. (2007). Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol Endocrinol 21:1028–1038.
  • Zhou, C., Verma, S., Blumberg, B. (2009). The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism. Nucl Recept Signal 7:e001.
  • Zhu, Z., Kim, S., Chen, T., Lin, J. H., Bell, A., Bryson, J., et al. (2004). Correlation of high-throughput pregnane X receptor (PXR) transactivation and binding assays. J Biomol Screen 9:533–540.
  • Zhu, Z., Puglisi, J., Connors, D., Stewart, J., Herbst, J., Marino, A., et al. (2007). Use of cryopreserved transiently transfected cells in high-throughput pregnane X receptor transactivation assay. J Biomol Screen 12:248–254.
  • Zimmermann, K., Wittman, M. D., Saulnier, M. G., Velaparthi, U., Sang, X., Frennesson, D. B., et al. (2010). SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors. Bioorg Med Chem Lett 20:1744–1748.

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