The potential pharmacological and toxicological impact of P450 screening

Current Opinion in Drug Discovery and Development

Volumn 4, Issue 1, 2001, Pages 45-54

  Riley, R J ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Automation; Cytochrome P450 (CYP); Drug interactions; Enhanced throughput; In vitro screening; Pharmacokinetics

Indexed keywords

COUMARIN DERIVATIVE; CYTOCHROME P450; CYTOCHROME P450 3A4; DIAZEPAM; DRUG; ERYTHROMYCIN; KETOCONAZOLE;

AUTOMATION; DRUG CLEARANCE; DRUG INTERACTION; DRUG METABOLISM; DRUG SCREENING; DRUG TOXICITY; DRUG TRANSFORMATION; ENZYME ACTIVITY; IC 50; INDIVIDUALIZATION; LIVER MICROSOME; PHARMACOKINETICS; PHYSICAL CHEMISTRY; REVIEW;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; DRUG EVALUATION, PRECLINICAL; DRUG INTERACTIONS; DRUG TOXICITY; HUMANS; MICROSOMES, LIVER;

EID: 0035154850     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (56)

1. Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964-1985)
2. High throughput drug metabolism
3. ADME/PK as part of a rational approach to drug discovery
4. Compound optimization in early- and latephase drug discovery: Acceptable pharmacokinetic properties utilizing combined physicochemical, in vitro and in vivo screens
5. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data
6. Allometric pharmacokinetic scaling: Towards the prediction of human oral pharmacokinetics
7. Improving the in vivo duration of 5-lipoxygenase inhibitors: Application of an in vitro glucuronosyltransferase assay
8. Quantitative estimation of hydrogen bond contribution to permeability and absorption processes of some chemicals and drugs
9. Prediction of human intestinal absorption of drug compounds from molecular structure
10. Applications and limitations of interspecies scaling and in vitro extrapolation in pharamcokinetics
11. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions
12. Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance
13. Prediction of hepatic clearance from microsomes, hepatocytes and liver slices
14. Merits and limitations of recombinant models for the study of human P450-mediated drug metabolism and toxicity: An intralaboratory comparison
15. Advances in in vitro drug metabolism screening
16. Automated definition of the enzymology of drug oxidation by the major human drug metabolising cytochromes P450 (CYPs)
17. On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: Towards the prediction of human P450 substrate specificity and metabolism
18. Polymorphic human cytochrome P450 enzymes: An opportunity for individualized drug treatment
19. Prediction of hepatic metabolic clearance based on interspecies allometric scaling techniques and in vitro-in vivo correlations
20. Pharmacokinetics and metabolism in early drug discovery
21. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes
22. Non specific binding of drugs to human liver mirosomes
23. In vitro-in vivo scaling of CYP kinetic data not consistent with the Michaelis-Menten model
24. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can bind simultaneously to cytochrome P450 active sites
25. Sigmoidal kinetics of CYP3A substrates: An approach for scaling dextromethorphan metabolism in hepatic microsomes and isolated hepatocytes to predict in vivo clearance in the rat
26. Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine
27. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies
28. Inhibition and induction of cytochrome P450 and the clinical implications
29. Terfenadine-ketoconazole interaction: Pharmacokinetic and electrocardiographic consequences
30. Cisapride and torsades de pointes
31. Drug-drug interactions of new active substances: Mibefradil example
32. Fully automated analysis of activities catalysed by the major human liver cytochrome P459 (CYP) enzymes: Assessment of human CYP inhibition potential
33. High throughput screening for inhibition of cytochrome P450 metabolism
34. Application of a generic fast gradient liquid chromatography tandem mass spectrometry method for the analysis of cytochrome P450 probe substrates
35. Automated high throughput human CYP isoform activity assay using SPE-LC/MS method: Application in CYP inhibition evaluation
36. CYP3A4 drug interactions: Correlation of 10 in vitro probe substrates
37. P-glycoprotein and cytochrome P450-3A inhibition: Dissociation of inhibitory properties
38. Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system
39. Effects of the antifungal agents on oxidative drug metabolism: Clinical relevance
40. Correlation between in vivo and in vitro hepatic uptake of metabolic inhibitors of cytochrome P450 in rats
41. Quantitative prediction of metabolic inhibition of midazolam by erythromycin, diltiazem, and verapamil in rats: Implication of concentrative uptake of inhibitors into liver
42. Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics: Use of maximum unbound concentration at the inlet to the liver
43. Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4
44. Relevance of induction of human drug metabolising enzymes: Pharmacological and toxicological implications
45. Induction of drug metabolising enzymes: Pharmacokinetic and toxicological consequences in humans
46. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions
47. St John's wort induces hepatic drug metabolism through activation of the pregnane X receptor
48. Measurement of cytochrome P450 gene induction in human hepatocytes using real-time reverse transcriptase-polymerase chain reaction
49. The aromatic hydrocarbon receptor, transcription, and endocrine aspects of dioxin action
50. P450 gene induction by structurally diverse xenochemicals: Central role of nuclear receptors CAR, PXR and PPAR
51. A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro
52. Regulation of the CYP3A4 gene by hydrocortisone and xenobiotics: Role of the glucocorticoid and pregnane X receptors
53. Two-stage glucocorticoid induction of CYP3A23 through both the glucocorticoid and pregnane X receptors
54. Dexamethasone induces pregnane X receptor and retinoid X receptor-α expression in human hepatocytes: Synergistic increase of CYP3A4 induction by pregnane X receptor activators