Pxr, car and drug metabolism (original) (raw)

• Nebert, D. W. & Gonzalez, F. J. P450 genes: structure, evolution, and regulation. Annu. Rev. Biochem. 56, 945–993 (1987).
  Article CAS PubMed Google Scholar
• Nelson, D. R. et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6, 1–42 (1996).
  Article CAS PubMed Google Scholar
• Denison, M. S. & Whitlock, J. P. Jr. Xenobiotic-inducible transcription of cytochrome P450 genes. J. Biol. Chem. 270, 18175–18178 (1995).
  Article CAS PubMed Google Scholar
• Selye, H. Hormones and resistance. J. Pharm. Sci. 60, 1–28 (1971).
  Article CAS PubMed Google Scholar
• Quattrochi, L. C. & Guzelian, P. S. CYP3A regulation: from pharmacology to nuclear receptors. Drug Metab. Dispos. 29, 615–622 (2001).
  CAS PubMed Google Scholar
• Kocarek, T. A., Schuetz, E. G., Strom, S. C., Fisher, R. A. & Guzelian, P. S. Comparative analysis of cytochrome P450 3A induction in primary cultures of rat, rabbit, and human hepatocytes. Drug Metab. Dispos. 23, 415–421 (1995).
  CAS PubMed Google Scholar
• Remmer, H. & Merker, H. Drug-induced changes in the liver endoplasmic reticulum — association with drug-metabolizing enzymes. Science 142, 16657–16658 (1963).
  Article Google Scholar
• Waxman, D. J. & Azaroff, L. Phenobarbital induction of cytochrome P450 gene expression. Biochem. J. 281, 577–592 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Waxman, D. J. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch. Biochem. Biophys. 369, 11–23 (1999).
  Article CAS PubMed Google Scholar
• Sueyoshi, T. & Negishi, M. Phenobarbital response elements of cytochrome P450 genes and nuclear receptors. Annu. Rev. Pharmacol. Toxicol. 41, 123–143 (2001).
  Article CAS PubMed Google Scholar
• Okey, A. B. Enzyme induction in the cytochrome P450 system. Pharmacol. Ther. 45, 241–298 (1990).
  Article CAS PubMed Google Scholar
• Michalets, E. L. Update: clinically significant cytochrome P450 drug interactions. Pharmacotherapy 18, 84–112 (1998).
  CAS PubMed Google Scholar
• Guengerich, F. P. Cytochrome P450 3A4: regulation and role in drug metabolism. Annu. Rev. Pharmacol. Toxicol. 39, 1–17 (1999).
  Article CAS PubMed Google Scholar
• Li, A. P., Kaminski, D. L. & Rasmussen, A. Substrates of human hepatic cytochrome P450 3A4. Toxicology 104, 1–8 (1995).
  Article CAS PubMed Google Scholar
• Veehof, L. J. G., Stewart, R. E., Meyboom-de Jong, B. & Haaijer-Ruskamp, F. M. Adverse drug reactions and polypharmacy in the elderly in general practice. Eur. J. Clin. Pharmacol. 55, 533–536 (1999).
  Article CAS PubMed Google Scholar
• Kuhlmann, J. & Muck, W. Clinical-pharmacological strategies to assess drug interaction potential during drug development. Drug Saf. 24, 715–725 (2001).
  Article CAS PubMed Google Scholar
• Gronemeyer, H. & Laudet, V. Transcription factors 3: nuclear receptors. Protein Profile 2, 1173–1308 (1995).
  CAS PubMed Google Scholar
• Kliewer, S. A., Lehmann, J. M. & Willson, T. M. Orphan nuclear receptors: shifting endocrinology into reverse. Science 284, 757–760 (1999).
  Article CAS PubMed Google Scholar
• Chawla, A., Repa, J. J., Evans, R. M. & Mangelsdorf, D. J. Nuclear receptors and lipid physiology: opening the X-files. Science 294, 1866–1870 (2001).
  Article CAS PubMed Google Scholar
• Kliewer, S. A. et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92, 73–82 (1998).The first paper to describe the cloning of PXR. The authors showed that PXR is expressed in the liver and intestine, activated by PCN, glucocorticoids and antiglucocorticoids, and binds to a response element that is conserved in CYP3A promoters.
  Article CAS PubMed Google Scholar
• Lehmann, J. M. et al. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 102, 1016–1023 (1998).This paper, together with references 22 and 23 , described the cloning of the human orthologue of PXR, and identified its role in mediating many common drug–drug interactions.
  Article CAS PubMed PubMed Central Google Scholar
• Bertilsson, G. et al. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc. Natl Acad. Sci. USA 95, 12208–12213 (1998).See reference 21.
  Article CAS PubMed PubMed Central Google Scholar
• Blumberg, B. et al. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. 12, 3195–3205 (1998).See reference 20 . The authors also propose that human PXR functions as a promiscuous xenobiotic receptor.
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, H. et al. Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation. Arch. Biochem. Biophys. 368, 14–22 (1999).
  Article CAS PubMed Google Scholar
• Savas, U., Wester, M. R., Griffin, K. J. & Johnson, E. F. Rabbit pregnane X receptor is activated by rifampicin. Drug Metab. Dispos. 28, 529–537 (2000).
  CAS PubMed Google Scholar
• Jones, S. A. et al. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol. Endocrinol. 14, 27–39 (2000).
  Article CAS PubMed Google Scholar
• Handschin, C., Podvinec, M. & Meyer, U. A. CXR, a chicken xenobiotic-sensing orphan nuclear receptor, is related to both mammalian pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Proc. Natl Acad. Sci. USA 97, 10769–10774 (in the press).
• Moore, L. B. et al. PXR, CAR, and BXR define three pharmacologically distinct classes of nuclear receptors. Mol. Endocrinol. (in the press).
• Escriva, H., Delaunay, F. & Laudet, V. Ligand binding and nuclear receptor evolution. Bioessays 22, 717–727 (2000).
  Article CAS PubMed Google Scholar
• Zhang, J. et al. The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 11, 555–572 (2001).
  Article CAS PubMed Google Scholar
• Hustert, E. et al. Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab. Dispos. 29, 1454–1459 (2001).
  CAS PubMed Google Scholar
• Baes, M. et al. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol. Cell. Biol. 14, 1544–1552 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Choi, H.-S. et al. Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. J. Biol. Chem. 272, 23565–23571 (1997).
  Article CAS PubMed Google Scholar
• Forman, B. M. et al. Androstane metabolites bind to and deactivate the nuclear receptor CAR-β. Nature 395, 612–615 (1998).This paper proposed that the testosterone metabolite 3α,5α-androstanol is a naturally occurring CAR ligand. The androstane decreased the constitutive activity of mouse CAR.
  Article CAS PubMed Google Scholar
• Mangelsdorf, D. J. et al. The nuclear receptor superfamily: the second decade. Cell 83, 835–839 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Beato, M., Herrlich, P. & Schuetz, G. Steroid hormone receptors: many actors in search of a plot. Cell 83, 851–857 (1995).
  Article CAS PubMed Google Scholar
• Moore, L. B. et al. St John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Natl Acad. Aci. USA 97, 7500–7502 (2000). | PubMed |Hyperforin, a constituent of the herbal remedy St John's wort, was shown to be a potent PXR activator. This study provided a molecular mechanism for the interaction of St John's wort with prescription drugs such as oral contraceptives.
  Article CAS Google Scholar
• Lu, A. Y., Somogyi, A., West, S., Kuntzman, R. & Conney, A. H. Pregnenolone-16α-carbonitrile: a new type of inducer of drug-metabolizing enzymes. Arch. Biochem. Biophys. 152, 457–462 (1972).
  Article CAS PubMed Google Scholar
• Goodwin, B., Hodgson, E. & Liddle, C. The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol. Pharmacol. 56, 1329–1334 (1999).
  Article CAS PubMed Google Scholar
• Staudinger, J. L. et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl Acad. Sci. USA 98, 3369–3374 (2001).This paper, together with reference 90 , reported that PXR is activated by toxic bile acids and is involved in the metabolism and removal of these harmful chemicals from the body.
  Article CAS PubMed PubMed Central Google Scholar
• Xie, W. et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 406, 435–439 (2000).Targeted disruption of the Pxr gene in mice was shown to abolish induction of Cyp3a11 in response to PCN and dexamethasone. Expression of human PXR in the Pxr −/− mice resulted in induction of Cyp3a11 by the human-specific PXR agonist rifampicin. Mice that expressed a constitutively active form of PXR were resistant to the anaesthetic and paralytic effects of the CYP substrates tribromoethanol and zoxazolamine.
  Article CAS PubMed Google Scholar
• Savas, U., Griffin, K. J. & Johnson, E. F. Molecular mechanisms of cytochrome P450 induction by xenobiotics: an expanded role for nuclear hormone receptors. Mol. Pharmacol. 56, 851–857 (1999).
  Article CAS PubMed Google Scholar
• Schuetz, E. G. Induction of cytochromes P450. Curr. Drug Metab. 2, 139–147 (2001).
  Article CAS PubMed Google Scholar
• Zelko, I. & Negishi, M. Phenobarbital-elicited activation of nuclear receptor CAR in induction of cytochrome P450 genes. Biochem. Biophys. Res. Commun. 277, 1–6 (2000).
  Article CAS PubMed Google Scholar
• Honkakoski, P., Zelko, I., Sueyoshi, T. & Negishi, M. The nuclear orphan receptor CAR–retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol. Cell. Biol. 18, 5652–5658 (1998).CAR was shown to bind as a heterodimer with RXR to a phenobarbital response element that is conserved in CYP2B genes. The concentration of CAR in the nuclei of hepatocytes was shown to increase in response to phenobarbital treatment.
  Article CAS PubMed PubMed Central Google Scholar
• Kawamoto, T. et al. Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol. Cell. Biol. 19, 6318–6322 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Zelko, I., Sueyoshi, T., Kawamoto, T., Moore, R. & Negishi, M. The peptide near the C terminus regulates receptor CAR nuclear translocation induced by xenochemicals in mouse liver. Mol. Cell. Biol. 21, 2838–2846 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Sueyoshi, T., Kawamoto, T., Zelko, I., Honkakoski, P. & Negishi, M. The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J. Biol. Chem. 274, 6043–6046 (1999).
  Article CAS PubMed Google Scholar
• Tzameli, I., Pissios, P., Schuetz, E. G. & Moore, D. D. The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR. Mol. Cell. Biol. 20, 2951–2958 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Moore, L. B. et al. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J. Biol. Chem. 275, 15122–15127 (2000).
  Article CAS PubMed Google Scholar
• Tzameli, I. & Moore, D. D. Role reversal: new insights from new ligands for the xenobiotic receptor CAR. Trends Endocrinol. Metab. 12, 7–10 (2001).
  Article CAS PubMed Google Scholar
• Wei, P., Zhang, J., Egan-Haffley, M., Liang, S. & Moore, D. D. The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 407, 920–923 (2000).Targeted disruption of the Car gene in mice was shown to abolish phenobarbital- and TCPOBOP-induced hepatomegaly and induction of Cyp2b10 expression. Car −/− mice were hypersensitive to paralysis caused by the CYP substrate zoxazolamine.
  Article CAS PubMed Google Scholar
• Weatherman, R. V., Fletterick, R. J. & Scanlan, T. S. Nuclear-receptor ligands and ligand-binding domains. Annu. Rev. Biochem. 68, 559–581 (1999).
  Article CAS PubMed Google Scholar
• Steinmetz, A. C. U., Renaud, J.-P. & Moras, D. Binding of ligands and activation of transcription by nuclear receptors. Annu. Rev. Biophys. Biomol. Struct. 30, 329–359 (2001).
  Article CAS PubMed Google Scholar
• Watkins, R. E. et al. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 292, 2329–2333 (2001).This paper described the three-dimensional structure of the PXR ligand-binding domain. The ligand-binding pocket was shown to be large and spherical in character, enabling it to function as a promiscuous xenobiotic receptor.
  Article CAS PubMed Google Scholar
• Wurtz, J.-M. et al. A canonical structure for the ligand-binding domain of nuclear receptors. Nature Struct. Biol. 3, 87–94 (1996).
  Article CAS PubMed Google Scholar
• Gillam, E. M. The PXR ligand-binding domain: how to be picky and promiscuous at the same time. Trends Pharmacol. Sci. 22, 448 (2001).
  Article CAS PubMed Google Scholar
• Dotzlaw, H., Leygue, E., Watson, P. & Murphy, L. C. The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin. Cancer Res. 5, 2103–2107 (1999).
  CAS PubMed Google Scholar
• Rochel, N., Wurtz, J. M., Mitschler, A., Klaholz, B. & Moras, D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 5, 173–179 (2000).
  Article CAS PubMed Google Scholar
• Moore, J. T. & Kliewer, S. A. Use of the nuclear receptor PXR to predict drug interactions. Toxicology 153, 1–10 (2000).
  Article CAS PubMed Google Scholar
• Fuhr, U. Induction of drug metabolizing enzymes: pharmacokinetic and toxicological consequences in humans. Clin. Pharmacokinet. 38, 493–504 (2000).
  Article CAS PubMed Google Scholar
• Watkins, P. B. & Whitcomb, R. W. Hepatic dysfunction associated with troglitazone. N. Engl. J. Med. 338, 916–917 (1998).
  Article CAS PubMed Google Scholar
• Yamazaki, H. et al. Oxidation of troglitazone to a quinone-type metabolite catalysed by cytochrome P450 2C8 and P450 3A4 in human liver microsomes. Drug Metab. Dispos. 27, 1260–1266 (1999).
  CAS PubMed Google Scholar
• He, K., Woolf, T. F., Kindt, E. K., Fielder, A. E. & Talaat, R. E. Troglitazone quinone formation catalysed by human and rat CYP3A: an atypical CYP oxidation reaction. Biochem. Pharmacol. 62, 191–198 (2001).
  Article CAS PubMed Google Scholar
• Kostrubsky, V. E. et al. Induction of cytochrome P450 3A by taxol in primary cultures of human hepatocytes. Arch. Biochem. Biophys. 15, 131–136 (1998).
  Article Google Scholar
• Synold, T. W., Dussault, I. & Forman, B. M. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nature Med. 7, 584–590 (2001).
  Article CAS PubMed Google Scholar
• LeCluyse, E. L. Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur. J. Pharm. Sci. 13, 343–368 (2001).
  Article CAS PubMed Google Scholar
• LeCluyse, E. L. Pregnane X receptor: molecular basis for species differences in CYP3A induction by xenobiotics. Chem. Biol. Interact. 134, 283–289 (2001).
  Article CAS PubMed Google Scholar
• Wentworth, J. M., Agostini, M., Love, J., Schwabe, J. W. & Chatterjee, V. K. K. St John's wort, a herbal antidepressant, activates the steroid X receptor. J. Endocrinol. 166, R11–R16 (2000).
  Article CAS PubMed Google Scholar
• Dussault, I. et al. Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J. Biol. Chem. 276, 33309–33312 (2001).
  Article CAS PubMed Google Scholar
• Xie, W. et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev. 14, 3014–3023 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Goodwin, B., Moore, L. B., Stoltz, C. M., McKee, D. D. & Kliewer, S. A. Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol. Pharmacol. 60, 427–431 (2001).
  CAS PubMed Google Scholar
• Handschin, C., Podvinec, M., Stockli, J., Hoffmann, K. & Meyer, U. A. Conservation of signaling pathways of xenobiotic-sensing orphan nuclear receptors, chicken xenobiotic receptor, constitutive androstane receptor, and pregnane X receptor, from birds to humans. Mol. Endocrinol. 15, 1571–1585 (2001).
  Article CAS PubMed Google Scholar
• Smirlis, D., Muangmoonchai, R., Edwards, M., Phillips, I. R. & Shephard, E. A. Orphan receptor promiscuity in the induction of cytochromes P450 by xenobiotics. J. Biol. Chem. 276, 12822–12826 (2001).
  Article CAS PubMed Google Scholar
• Wei, P., Zhang, J., Dowhan, D. H., Han, Y. & Moore, D. D. Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response. Pharmacogenomics J. (in the press) .
• Guengerich, F. P. Pharmacogenomics of cytochrome P450 and other enzymes involved in biotransformation of xenobiotics. Drug Dev. Res. 49, 4–16 (2000).
  Article CAS Google Scholar
• Meyer, U. A. Pharmacogenetics and adverse drug reactions. Lancet 356, 1667–1671 (2000).
  Article CAS PubMed Google Scholar
• Evans, W. E. & Johnson, J. A. Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu. Rev. Genomics Hum. Genet. 2, 9–39 (2001).
  Article CAS PubMed Google Scholar
• Ekins, S. & Erickson, J. A. A pharmacophore for human pregnane X receptor ligands. Drug Metab. Dispos. 30, 96–99 (2002).
  Article CAS PubMed Google Scholar
• Bohm, H.-J. & Stahl, M. Structure-based library design: molecular modeling merges with combinatorial chemistry. Curr. Opin. Chem. Biol. 4, 283–286 (2000).
  Article CAS PubMed Google Scholar
• Leach, A. R. & Hann, M. M. The in silico world of virtual libraries. Drug Discov Today 5, 326–336 (2000).
  Article CAS PubMed Google Scholar
• Fox, S., Wang, H., Sopchak, L. & Khoury, R. High throughput screening: early successes indicate a promising future. J. Biomol. Screening 6, 137–140 (2001).
  Article CAS Google Scholar
• Lazar, M. A. Gene regulation: one man's food. Nature 407, 852–853 (2000).
  Article CAS PubMed Google Scholar
• Gillam, E. Transgenic xenosensors: humanizing mice. Trends Pharmacol. Sci. 21, 330–331 (2000).
  Article CAS PubMed Google Scholar
• Maglich, J. M. et al. Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drospohila genomes. Genome Biol. [online] (cited 12 Feb 2002) 〈http://genomebiology.com/2001/2/8/research/0029/〉 (2001).
• Muerhoff, A. S., Griffin, K. J. & Johnson, E. F. The peroxisome proliferator-activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid ω-hydroxylase, by clofibric acid. J. Biol. Chem. 267, 19051–19053 (1992).
  CAS PubMed Google Scholar
• Kroetz, D. L., Yook, P., Costet, P., Bianchi, P. & Pineau, T. Peroxisome proliferator-activated receptor α controls the hepatic CYP4A induction adaptive response to starvation and diabetes. J. Biol. Chem. 273, 31581–31589 (1998).
  Article CAS PubMed Google Scholar
• Takeyama, K. et al. 25-Hydroxyvitamin D3 1α-hydroxylase and vitamin D synthesis. Science 277, 1827–1830 (1997).
  Article CAS PubMed Google Scholar
• Murayama, A. et al. The promoter of the human 25-hydroxyvitamin D3 1α-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1α,25(OH)2D3 . Biochem. Biophys. Res. Commun. 249, 11–16 (1998).
  Article CAS PubMed Google Scholar
• Xie, W. et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Natl Acad. Sci. USA 98, 3375–3380 (2001).See reference 40.
  Article CAS PubMed PubMed Central Google Scholar
• Ueda, A. et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol. Pharmacol. 61, 1–6 (2002).
  Article CAS PubMed Google Scholar
• Willson, T. M., Jones, S. A., Moore, J. T. & Kliewer, S. A. Chemical genomics: functional analysis of orphan nuclear receptors in the regulation of bile acid metabolism. Med. Res. Rev. 21, 513–522 (2001).
  Article CAS PubMed Google Scholar
• Geick, A., Eichelbaum, M. & Burk, O. Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J. Biol. Chem. 276, 14581–14587 (2001).
  Article CAS PubMed Google Scholar
• Guo, G. L., Choudhuri, S. & Klaassen, C. D. Induction profile of rat organic anion transporting polypeptide 2 (Oatp2) by prototypical drug-metabolizing enzyme inducers that activate gene expression through ligand-activated transcription factor pathways. J. Pharmacol. Exp. Ther. 300, 206–212 (2002).
  Article CAS PubMed Google Scholar
• Kast, H. R. et al. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X receptor, and constitutive androstane receptor. J. Biol. Chem. 277, 2908–2915 (2002).
  Article CAS PubMed Google Scholar
• Borst, P., Evers, R., Kool, M. & Wijnholds, J. A family of drug transporters: the multidrug resistance-associated proteins. J. Natl Cancer Inst. 92, 1295–1302 (2000).
  Article CAS PubMed Google Scholar
• Gao, B. & Meier, P. J. Organic anion transport across the choroid plexus. Microsc. Res. Tech. 52, 60–64 (2001).
  Article CAS PubMed Google Scholar
• Kerb, R., Hoffmeyer, S. & Brinkmann, U. ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics 2, 51–64 (2001).
  Article CAS PubMed Google Scholar
• Suzuki, H. & Sugiyama, Y. Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine. Eur. J. Pharm. Sci. 12, 3–12 (2000).
  Article CAS PubMed Google Scholar
• Hofmann, A. F. The continuing importance of bile acids in liver and intestinal disease. Arch. Intern. Med. 159, 2647–2658 (1999).
  Article CAS PubMed Google Scholar
• Staudinger, J., Liu, Y., Madan, A., Habeebu, S. & Klaassen, C. D. Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Drug Metab. Dispos. 29, 1467–1472 (2001).
  CAS PubMed Google Scholar
• Chevallier, A. The Encyclopedia of Medicinal Plants (Dorling Kindersley, New York, 1996).
  Google Scholar
• Nuclear Receptors Committee. A unified nomenclature system for the nuclear receptor superfamily. Cell 97, 161–163 (1999).