Enzyme- and transporter-based drug-drug Interactions : progress and future challenges

Enzyme systems have evolved in humans to maintain cellular homeostasis and to facilitate the disposition of xenobiotics. These enzymes possess complementary, and sometimes overlapping, functions, a feature which can set the stage for drug–drug interactions. In this chapter, we provide an overview of the phase I and phase II families of detoxification enzymes, their potential for induction and inhibition, and the role of genetic variants in the occurrence of drug–drug interactions. 1.

[1]  P. Mackenzie,et al.  INHIBITION OF UDP-GLUCURONOSYLTRANSFERASE 2B7-CATALYZED MORPHINE GLUCURONIDATION BY KETOCONAZOLE: DUAL MECHANISMS INVOLVING A NOVEL NONCOMPETITIVE MODE , 2006, Drug Metabolism and Disposition.

[2]  Georges de Sousa,et al.  A PXR reporter gene assay in a stable cell culture system: CYP3A4 and CYP2B6 induction by pesticides. , 2004, Biochemical pharmacology.

[3]  D. Moody,et al.  Differential N-demethylation of l-alpha-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18, and 3A4. , 2001, Biochemical and biophysical research communications.

[4]  J M Ward,et al.  Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice. , 1998, Toxicology and applied pharmacology.

[5]  D. E. Clark,et al.  PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores. , 1994, Journal of medicinal chemistry.

[6]  K. Yoshinari,et al.  Assessment of Human Pregnane X Receptor Involvement in Pesticide-Mediated Activation of CYP3A4 Gene , 2007, Drug Metabolism and Disposition.

[7]  Edith Sim,et al.  Arylamine N-acetyltransferases: from structure to function. , 2008, Drug metabolism reviews.

[8]  I. Phillips,et al.  The molecular biology of the flavin-containing monooxygenases of man. , 1995, Chemico-biological interactions.

[9]  M. Shimizu,et al.  Effect of Genetic Variants of the Human Flavin-Containing Monooxygenase 3 on N- and S-Oxygenation Activities , 2007, Drug Metabolism and Disposition.

[10]  F. Nagengast,et al.  Biotransformation enzymes in human intestine: critical low levels in the colon? , 1991, Gut.

[11]  E. Gillam,et al.  Differential inhibition of human liver phenacetin O-deethylation by histamine and four histamine H2-receptor antagonists. , 1988, Xenobiotica; the fate of foreign compounds in biological systems.

[12]  Karthik Venkatakrishnan,et al.  Human Drug Metabolism and the Cytochromes P450: Application and Relevance of In Vitro Models , 2001, Journal of clinical pharmacology.

[13]  J. Snawder,et al.  Loss of CYP2E1 and CYP1A2 activity as a function of acetaminophen dose: relation to toxicity. , 1994, Biochemical and biophysical research communications.

[14]  M. Murray,et al.  Participation of CYP2C8 in retinoic acid 4-hydroxylation in human hepatic microsomes. , 1999, Biochemical pharmacology.

[15]  Gourdas Choudhuri,et al.  Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis. , 2009, Mutation research.

[16]  K Farrell,et al.  Identification and characterization of the glutathione and N-acetylcysteine conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans. , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[17]  H. Derendorf,et al.  Hyperforin in St. John’s wort drug interactions , 2006, European Journal of Clinical Pharmacology.

[18]  S Ohmori,et al.  Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. , 1994, Drug metabolism and disposition: the biological fate of chemicals.

[19]  A. Farcomeni,et al.  Valproic Acid Induces Neuroendocrine Differentiation and UGT2B7 Up-Regulation in Human Prostate Carcinoma Cell Line , 2007, Drug Metabolism and Disposition.

[20]  M. Wester,et al.  Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. , 1998, Archives of biochemistry and biophysics.

[21]  J. Fahey,et al.  Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. , 2001, The Journal of nutrition.

[22]  J. Cashman,et al.  Two new polymorphisms of the FMO3 gene in Caucasian and African-American populations: comparative genetic and functional studies. , 2003, Drug metabolism and disposition: the biological fate of chemicals.

[23]  Fernando Rodrigues-Lima,et al.  Identification of the Xenobiotic-Metabolizing Enzyme Arylamine N-Acetyltransferase 1 as a New Target of Cisplatin in Breast Cancer Cells: Molecular and Cellular Mechanisms of Inhibition , 2008, Molecular Pharmacology.

[24]  J. Pascussi,et al.  The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. , 2003, Biochimica et biophysica acta.

[25]  J T Slattery,et al.  Dose‐dependent pharmacokinetics of acetaminophen: Evidence of glutathione depletion in humans , 1987, Clinical pharmacology and therapeutics.

[26]  T. Omura,et al.  Forty years of cytochrome P450. , 1999, Biochemical and biophysical research communications.

[27]  T. Shimada,et al.  Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice. , 2002, Carcinogenesis.

[28]  S. Amin,et al.  Glucuronidation of Active Tamoxifen Metabolites by the Human UDP Glucuronosyltransferases , 2007, Drug Metabolism and Disposition.

[29]  P. Neuvonen,et al.  In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. , 2008, Basic & clinical pharmacology & toxicology.

[30]  R. Obach,et al.  Examination of 209 Drugs for Inhibition of Cytochrome P450 2C8 , 2005, Journal of clinical pharmacology.

[31]  R. Weinshilboum,et al.  Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity. , 1989, Genetics.

[32]  M. Schwab,et al.  Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. , 2007, Pharmacogenomics.

[33]  Ronald N Hines,et al.  Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants , 2007, Journal of Pharmacology and Experimental Therapeutics.

[34]  J. Sahi,et al.  Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. , 2003, Drug metabolism and disposition: the biological fate of chemicals.

[35]  T. Skaar,et al.  Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen , 2005, Cancer Chemotherapy and Pharmacology.

[36]  H. Yamazaki,et al.  In vitro inhibitory effects of troglitazone and its metabolites on drug oxidation activities of human cytochrome P450 enzymes: comparison with pioglitazone and rosiglitazone. , 2000, Xenobiotica; the fate of foreign compounds in biological systems.

[37]  T. Iga,et al.  INVOLVEMENT OF CYP 2 B 6 IN N-DEMETHYLATION OF KETAMINE IN HUMAN LIVER MICROSOMES , 2001 .

[38]  G. Pacifici.  Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature. , 2004, International journal of clinical pharmacology and therapeutics.

[39]  R. Weinshilboum,et al.  Sulfotransferase molecular biology: cDNAs and genes , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  M. Ingelman-Sundberg,et al.  Generation of Mice Transgenic for Human CYP2C18 and CYP2C19: Characterization of the Sexually Dimorphic Gene and Enzyme Expression , 2008, Drug Metabolism and Disposition.

[41]  M. Brodie,et al.  Assay and characterisation of debrisoquine 4-hydroxylase activity of microsomal fractions of human liver. , 1982, British journal of clinical pharmacology.

[42]  D. Grant,et al.  N-acetylation pharmacogenetics: a gene deletion causes absence of arylamine N-acetyltransferase in liver of slow acetylator rabbits. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[43]  M. Chandy,et al.  Glutathione S-transferase activity influences busulfan pharmacokinetics in patients with beta thalassemia major undergoing bone marrow transplantation. , 2001, Drug metabolism and disposition: the biological fate of chemicals.

[44]  Anna M. Lee,et al.  CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial , 2007, Biological Psychiatry.

[45]  K. Otani,et al.  Interaction Study Between Enoxacin and Fluvoxamine , 2005, Therapeutic drug monitoring.

[46]  S. Strom,et al.  Expression and Induction of CYP2C P450 Enzymes in Primary Cultures of Human Hepatocytes , 2002, Journal of Pharmacology and Experimental Therapeutics.

[47]  I. Roots,et al.  Differential drug-induced mRNA expression of human CYP3A4 compared to CYP3A5, CYP3A7 and CYP3A43. , 2003, European journal of pharmacology.

[48]  J. Idle,et al.  POLYMORPHIC HYDROXYLATION OF DEBRISOQUINE IN MAN , 1977, The Lancet.

[49]  P. Neuvonen,et al.  GEMFIBROZIL INHIBITS CYP 2 C 8-MEDIATED CERIVASTATIN METABOLISM IN HUMAN LIVER MICROSOMES , 2002 .

[50]  H. Yamazaki,et al.  Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. , 1994, The Journal of pharmacology and experimental therapeutics.

[51]  P. van Bladeren,et al.  Quantification of human hepatic glutathione S-transferases. , 1990, The Biochemical journal.

[52]  S. Lory,et al.  The activities of several detoxication enzymes are differentially induced by juices of garden cress, water cress and mustard in human HepG2 cells. , 2004, Chemico-biological interactions.

[53]  H. Satoh,et al.  Substrate dependent inhibition profiles of fourteen drugs on CYP3A4 activity measured by a high throughput LCMS/MS method with four probe drugs, midazolam, testosterone, nifedipine and terfenadine. , 2003, Drug metabolism and pharmacokinetics.

[54]  R. Weinshilboum,et al.  Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. , 1997, Biochemical and biophysical research communications.

[55]  A. Nishikawa,et al.  Effect of cigarette smoke on the mutagenic activation of various carcinogens in hamster. , 1996, Mutation research.

[56]  Zeruesenay Desta,et al.  Endoxifen, a Secondary Metabolite of Tamoxifen, and 4-OH-Tamoxifen Induce Similar Changes in Global Gene Expression Patterns in MCF-7 Breast Cancer Cells , 2006, Journal of Pharmacology and Experimental Therapeutics.

[57]  A. J. Robinson,et al.  Warfarin analog inhibition of human CYP2C9-catalyzed S-warfarin 7-hydroxylation. , 1997, Thrombosis research.

[58]  P. Neuvonen,et al.  Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia , 2000, European Journal of Clinical Pharmacology.

[59]  S. Mitchell.  Flavin mono-oxygenase (FMO)--the 'other' oxidase. , 2008, Current drug metabolism.

[60]  E. Nieves,et al.  Subunit diversity and tissue distribution of human glutathione S-transferases: interpretations based on electrospray ionization-MS and peptide sequence-specific antisera. , 1997, The Biochemical journal.

[61]  S. Landi.  Mammalian class theta GST and differential susceptibility to carcinogens: a review. , 2000, Mutation research.

[62]  P. C. Lee,et al.  Metabolism of nonylphenol by rat and human microsomes. , 1998, Toxicology letters.

[63]  Michael D. Johnson,et al.  Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. , 2001, The Journal of pharmacology and experimental therapeutics.

[64]  J. Schuetz,et al.  Identification of the fetal liver cytochrome CYP3A7 in human endometrium and placenta. , 1993, The Journal of clinical investigation.

[65]  R. Kato,et al.  Genetic polymorphisms in human liver phenol sulfotransferases involved in the bioactivation of N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines. , 1998, Chemico-biological interactions.

[66]  D. G. Walters,et al.  Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. , 2004, Carcinogenesis.

[67]  David E. Williams,et al.  Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism. , 2005, Pharmacology & therapeutics.

[68]  T. Walle,et al.  Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in the human hepatoma cell line hep G2. , 2000, Drug metabolism and disposition: the biological fate of chemicals.