Use of in vitro human metabolism studies in drug development. An industrial perspective

Biochemical Pharmacology

Volumn 48, Issue 12, 1994, Pages 2147-2156

  David Rodrigues, A ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

drug development; drug metabolism models; drug metabolizing enzymes; human drug metabolism; in vitro methods; in vitro in vivo correlations

Indexed keywords

1 NAPHTHOL; 4 METHYLPYRAZOLE; ALPHA NAPHTHOFLAVONE; BENZALDEHYDE; COUMARIN; CYTOCHROME P450 ISOENZYME; DEXTROMETHORPHAN; DIETHYLDITHIOCARBAMIC ACID; DIMETHYLNITROSAMINE; DRUG METABOLIZING ENZYME; ENZYME INDUCING AGENT; ENZYME INHIBITOR; ERYTHROMYCIN; FURAFYLLINE; GESTODENE; KETOCONAZOLE; MEPHENYTOIN; PHENOBARBITAL; PHENYTOIN; QUINIDINE; RIFAMPICIN; SULFAPHENAZOLE; THEOPHYLLINE; TOLBUTAMIDE; TROLEANDOMYCIN; UNINDEXED DRUG; WARFARIN;

ANIMAL TISSUE; DRUG DEVELOPMENT; DRUG INDUSTRY; DRUG INTERACTION; DRUG METABOLISM; DRUG SCREENING; ENZYME INDUCTION; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER MICROSOME; MODEL; NONHUMAN; PREDICTION; PRIORITY JOURNAL; REVIEW; SPECIES DIFFERENCE; XENOBIOTIC METABOLISM;

CYTOCHROME P-450 ENZYME SYSTEM; DRUG INDUSTRY; DRUG INTERACTIONS; HUMAN; IN VITRO; ISOENZYMES; LIVER; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; SUBCELLULAR FRACTIONS; TISSUE DONORS;

EID: 0028114740     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/0006-2952(94)00312-2     Document Type: Article

References (83)

1. Use of human hepatocyte cultures for drug metabolism studies
2. The use of human liver for foreign compound metabolism and toxicity studies
3. Validation and use of cloned, expressed human drug-metabolizing enzymes in heterologous cells for analysis of drug metabolism and drug-drug interactions
4. Techniques for pharmacological and toxicological studies with isolated hepatocyte suspensions
5. cDNA-expressed human cytocheome P450s: A new age of molecular toxicology and human risk assessment
6. Tissue slicing and culturing revisited
7. The UDP-glucuronosyltransferase gene superfamily: Suggested nomenclature based on evolutionary divergence
8. The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature
9. Oxidation of the antihistaminic drug terfenadine in human liver microsomes
10. Terfenadineketoconazole interaction
11. Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin
12. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450
13. In vitro approaches can predict human drug metabolism
14. Understanding consequences of concurrent therapies
15. The use of in vitro metabolism studies in the understanding of new drugs
16. The rational selection of drug interaction studies: Implications of recent advances in drug metabolism
17. The role of individual human cytochromes P-450 in drug metabolism and clinical response
18. Stereoselective and isozyme-selective drug interactions
19. Speculations on the substrate structure-activity relationship (SSAR) of cytochrome P-450 enzymes
20. Characterization of human cytochrome P450 enzymes
21. The human hepatic cytochromes P450 involved in drug metabolism
22. Human cytochromes P450: Problems and prospects
23. Development of human liver UDP-glucuronosyltransferase
24. The expression of UDP-glucuronosyltransferases of the UGT1 family in human liver and kidney and in response to drugs
25. Interindividual variability of carbonyl reductase levels in human livers
26. Dimethylaniline N-oxidase and aminopyrine N-demethylase activities of human liver tissue
27. Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics
28. Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes
29. Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: Relationship to the presence of immunoidentified cytochrome P-450IID1
30. Inhibition by fluoxetine of cytochrome P-450 2D6 activity
31. Effect of age and gender on the activity of human hepatic CYP3A
32. Metabolism of N-nitrosodialkylamines by human liver microsomes.
33. Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1
34. Human P450 enzymes associated with the mephenytoin 4-hydroxylation polymorphism
35. 14C]dextromethorphan
36. Metabolism of nicotine
37. Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism
38. Bioavailability of terfenadine in man
39. The hepatic first-pass metabolism of problematic drugs
40. High-performance liquid chromatographic assays for bufuralol 1′-hydroxylase, debrisoquine 4-hydroxylase, and dextromethorphan O-demethylase in microsomes and purified cytochrome P-450 isozymes of human liver
41. Characteristics of warfarin hydroxylation catalyzed by human liver microsomes
42. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: A role for P-4502C9 in the etiology of (S)-warfarin-drug interactions
43. Development of a simple incubation system for metabolism studies with precision-cut liver slices
44. A new instrument for the rapid preparation of tissue slices
45. Cryopreservation of human adult hepatocytes for use in drug metabolism and toxicity studies
46. Species differences in metabolism of ketotifen in rat, rabbit and man: Demonstration of similar pathways in vivo and in cultured hepatocytes
47. Comparative drug metabolism of diazepam in hepatocytes isolated from man, rat, monkey and dog
48. Human and dog, but not rat, isolated hepatocytes have decreased foreign compound-metabolizing activity compared to liver slices
49. Cultured human adult hepatocytes: A new model for drug metabolism studies
50. Cyclosporin A metabolism in human liver, kidney, and intestine slices
51. A species comparison of tolbutamide metabolism in precision-cut liver slices from rats and dogs
52. Species variation in hepatic aldehyde oxidase activity
53. Human liver aldehyde oxidase: Differential inhibition of oxidation of charged and uncharged substrates
54. Species-dependent glucuronidation of drugs by immobilized rabbit, rhesus monkey, and human UDP-glucuronosyltransferases
55. Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: Effects on coumarin, dicumarol and testoterone oxidation
56. Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1
57. Human liver microsomal cytochrome P-450 enzymes involved in the bioactivation of procarcinogens detected by umu gene response in Salmonella typhimurium TA 1535/pSK1002
58. Characterization of cytochrome P-450 2B6 in human liver microsomes
59. Two monoclonal antibodies recognizing different epitopes on rat cytochrome IIB1 react with human IIE1
60. Isoform-selective mechanism-based inhibition of human cytochrome P450 1A2 by furafylline
61. Furafylline is a potent and selective inhibitor of cytochrome P-450IA2 in man
62. Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2
63. PA (P-4501A2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines
64. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects
65. Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes
66. Oxidation of quinidine by human liver cytochrome P-450
67. Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes
68. Tolbutamide hydroxylation by human liver microsomes
69. Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene
70. Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture
71. Inhibition of human hepatic and placental xenobiotic monooxygenases by imidazole antimycotics
72. Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes
73. Enzyme induction and inhibition
74. Clinical implications of enzyme induction and enzyme inhibition
75. Enzyme induction in the cytochrome P-450 system
76. Effect of xenobiotics on monooxygenase activities in cultured human hepatocytes
77. Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes
78. Effects of various inducers on the expression of cytochromes P-450IIC8, 9, 10 and IIIA in cultured adult human hepatocytes
79. The effects of inducing agents on cytochrome P-450 and UDP-glucuronosyltransferase activities in human HepG2 hepatoma cells
80. Comparison of cytochrome P450 isoenzyme profiles in rat liver and hepatocyte cultures
81. Human adult hepatocytes in primary monolayer culture
82. Maintenance of cytochrome P-450 in cultured adult human hepatocytes
83. Trends in pharmaceutical development