Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin

Drug Metabolism and Disposition

Volumn 28, Issue 11, 2000, Pages 1369-1378

  Jacobsen, Wolfgang ^a   Kuhn, Bernd ^a   Soldner, Andrea ^a   Kirchner, Gabriele ^b   Sewing, Karl Fr ^b   Kollman, Peter A ^a   Benet, Leslie Z ^a   Christians, Uwe ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXYATORVASTATIN; 4 HYDROXYATORVASTATIN; ATORVASTATIN; BMS 241423 01; BMS 241424 01; BMS 243887 01; BMS 2438883 01; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; CYTOCHROME P450 ISOENZYME; DRUG METABOLITE; LACTONE; PD 142542; PD 152873; UNCLASSIFIED DRUG;

ARTICLE; DRUG DISPOSITION; HUMAN; HUMAN CELL; LIVER MICROSOME METABOLISM; METABOLIC CLEARANCE RATE; MICHAELIS MENTEN KINETICS; PRIORITY JOURNAL;

DNA, COMPLEMENTARY; HEPTANOIC ACIDS; HUMANS; HYDROXYLATION; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LACTONES; MICROSOMES, LIVER; PYRROLES;

EID: 0033783036     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (43)

1. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges - The RESP model
2. 50) of an enzymatic reaction
3. Metabolism and drug interactions of HMG-CoA reductase inhibitors in transplant patients. Are the statins mechanistically similar?
4. Simultaneous on-line analysis of drugs in blood by liquid chromatography/electrospray mass spectrometry
5. Study on the regioselectivity and mechanism of the aromatic hydroxylation of monofluoroanilines
6. Valproic acid metabolism by cytochrome-P450 - A theoretical study of stereoelectronic modulators of product distribution
7. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules
8. Selectively deuterated warfarin - Substrate probe for the mechanism of aromatic hydroxylation catalyzed by cytochrome P450
9. The measurement of difference spectra: Application to the cytochromes of microsomes
10. Critical evaluation of search algorithms for automated molecular docking and database screening
11. Selective biotransformation of the human immunodeficiency vires protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4
12. Application of the RESP methodology in the parameterization of organic solvents
13. Thioanisole sulfoxidation by cytochrome P450(Cam) (Cyp101) -Experimental and calculated absolute stereochemistries
14. Effects of hepatic and renal impairment on pharmacokinetics (PK) and pharmacodynamics (PD) of atorvastatin
15. Metabolism of lovastatin by rat and human liver microsomes in vitro
16. Microsomal enzymes involved in toxicology - Analysis and separation
17. Human cytochrome P450 enzymes
18. Prediction of regiospecific hydroxylation of camphor analogs by cytochrome P450(Cam)
19. Comparison of simple potential functions for simulating liquid water
20. Effect of itraconazole on the pharmacokinetics of atorvastatin
21. The interconversion kinetics, equilibrium, and solubilities of the lactone and hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981
22. Electron affinities of the 1st-row atoms revisited - Systematic basis sets and wave functions
23. A ligand is predicted to bind better to avidin than biotin: Insights from computational fluorine scanning
24. In vitro and in vivo metabolism of atorvastatin (CI-981)
25. On the membrane topology of vertebrate cytochrome-P-450 proteins
26. Secondary structure prediction of 52 membrane-bound cytochromes-P450 shows a strong structural similarity to P450cam
27. Itraconazole drastically increase plasma concentration of lovastatin and lovastatin acid
28. Simvastatin, but not pravastatin, is very susceptible to interact with the CYP3A inhibitor itraconazole
29. Oxygen activation and reactivity
30. Controlling the regiospecificity and coupling of cytochrome P450cam - T185f mutant increases coupling and abolishes 3-hydroxynorcamphor product
31. Predicting the product specificity and coupling of cytochrome P450cam
32. Bacterial P450s. Structural similarities and functional differences
33. Regioselectivity of cytochrome-P-450 catalyzed hydroxylation of fluorobenzenes predicted by calculated frontier orbital substrate characteristics
34. Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes
35. Mechanism of cytochrome P450-catalyzed aromatic hydroxylation of estrogens
36. Measurement of protein using bicinchoninic acid
37. Continuum solvent studies of the stability of DNA, RNA and phosphoramidate-DNA helices
38. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields
39. Molecular modeling of cytochrome P450 3A4
40. Molecular basis of P450 inhibition and activation - Implications for drug development and drug therapy
41. Molecular orbital study of the hydroxylation of benzene and monofluorobonzene catalyzed by iron-oxoporphyrin Pi cation radical complexes
42. Molecular orbital study of porphyrin-substrate interactions in cytochrome P450 catalyzed aromatic hydroxylation of substituted anilines