Characterization of ritonavir-mediated inactivation of cytochrome P450 3A4

Molecular Pharmacology

Volumn 86, Issue 6, 2014, Pages 665-674

  Rock, Brooke M ^a   Hengel, Shawna M ^b   Rock, Dan A ^a   Wienkers, Larry C ^a   Kunze, Kent L ^b,c  

^a AMGEN INC   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c Bioanalytical Development Seattle Genetics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APOPROTEIN; CYTOCHROME P450 3A4; LYSINE; RITONAVIR; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A; CYTOCHROME P450 3A INHIBITOR;

ARTICLE; COMPETITIVE INHIBITION; COMPLEX FORMATION; CONTROLLED STUDY; COVALENT BOND; DRUG EFFICACY; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; NUCLEOPHILICITY; PROTEIN DEGRADATION; STOICHIOMETRY; TANDEM MASS SPECTROMETRY; CHEMISTRY;

CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 CYP3A INHIBITORS; HUMANS; RITONAVIR;

EID: 84912050109     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.114.094862     Document Type: Article

References (37)

1. Baer BR, Wienkers LC, and Rock DA (2007) Time-dependent inactivation of P450 3A4 by raloxifene: identification of Cys239 as the site of apoprotein alkylation. Chem Res Toxicol 20:954-964.
2. Begriche K, Massart J, Robin MA, Borgne-Sanchez A, and Fromenty B (2011) Druginduced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol 54:773-794.
3. Bensoussan C, Delaforge M, and Mansuy D (1995) Particular ability of cytochromes P450 3A to form inhibitory P450-iron-metabolite complexes upon metabolic oxidation of aminodrugs. Biochem Pharmacol 49:591-602.
4. Blobaum AL, Kent UM, Alworth WL, and Hollenberg PF (2002) Mechanism-based inactivation of cytochromes P450 2E1 and 2E1 T303A by tert-butyl acetylenes: characterization of reactive intermediate adducts to the heme and apoprotein. Chem Res Toxicol 15:1561-1571.
5. Delaforge M, Jaouen M, and Mansuy D (1984) The cytochrome P-450 metabolite complex derived from troleandomycin: properties in vitro and stability in vivo. Chem Biol Interact 51:371-376.
6. Denissen JF, Grabowski BA, Johnson MK, Buko AM, Kempf DJ, Thomas SB, and Surber BW (1997) Metabolism and disposition of the HIV-1 protease inhibitor ritonavir (ABT-538) in rats, dogs, and humans. Drug Metab Dispos 25:489-501.
7. Ernest CS, 2nd, Hall SD, and Jones DR (2005) Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther 312:583-591.
8. Fernández-Montero JV, Barreiro P, and Soriano V (2009) HIV protease inhibitors: recent clinical trials and recommendations on use. Expert Opin Pharmacother 10:1615-1629.
9. Fletcher CV, Acosta EP, Cheng H, Haubrich R, Fischl M, Raasch R, Mills C, Hu XJ, Katzenstein D, and Remmel RP et al.; ACTG Protocol Team (2000) Competing drug-drug interactions among multidrug antiretroviral regimens used in the treatment of HIV- infected subjects: ACTG 884. AIDS 14:2495-2501.
10. Gan LS, Acebo AL, and Alworth WL (1984) 1-Ethynylpyrene, a suicide inhibitor of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity in liver microsomes. Biochemistry 23:3827-3836.
11. Halpert J (1982) Further studies of the suicide inactivation of purified rat liver cytochrome P-450 by chloramphenicol. Mol Pharmacol 21:166-172.
12. He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF, and Hollenberg PF (1998) Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 11:252-259.
13. HirschMS, GünthardHF, Schapiro JM, Brun-Vézinet F, Clotet B, Hammer SM, Johnson VA, Kuritzkes DR, Mellors JW, and Pillay D et al.; International AIDS Society-USA (2008) Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Top HIV Med 16:266-285.
14. Kempf DJ, Marsh KC, Kumar G, Rodrigues AD, Denissen JF, McDonald E, Kukulka MJ, Hsu A, Granneman GR, and Baroldi PA et al. (1997) Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother 41:654-660.
15. Koudriakova T, Iatsimirskaia E, Utkin I, Gangl E, Vouros P, Storozhuk E, Orza D, Marinina J, and Gerber N (1998) Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. Drug Metab Dispos 26:552-561.
16. Kumar GN, Rodrigues AD, Buko AM, and Denissen JF (1996) Cytochrome P450- mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther 277:423-431.
17. Kunze KL, Mangold BL, Wheeler C, Beilan HS, and Ortiz de Montellano PR (1983) The cytochrome P-450 active site. Regiospecificity of prosthetic heme alkylation by olefins and acetylenes. J Biol Chem 258:4202-4207.
18. Labbe G, Descatoire V, Beaune P, Letteron P, Larrey D, and Pessayre D (1989) Suicide inactivation of cytochrome P-450 by methoxsalen. Evidence for the covalent binding of a reactive intermediate to the protein moiety. J Pharmacol Exp Ther 250:1034-1042.
19. Lightning LK, Jones JP, Friedberg T, Pritchard MP, Shou M, Rushmore TH, and Trager WF (2000) Mechanism-based inactivation of cytochrome P450 3A4 by L-754,394. Biochemistry 39:4276-4287.
20. Lin HL and Hollenberg PF (2007) The inactivation of cytochrome P450 3A5 by 17alpha-ethynylestradiol is cytochrome b5-dependent: metabolic activation of the ethynyl moiety leads to the formation of glutathione conjugates, a heme adduct, and covalent binding to the apoprotein. J Pharmacol Exp Ther 321:276-287.
21. Lin HL, D'Agostino J, Kenaan C, Calinski D, and Hollenberg PF (2013) The effect of ritonavir on human CYP2B6 catalytic activity: heme modification contributes to the mechanism-based inactivation of CYP2B6 and CYP3A4 by ritonavir. Drug Metab Dispos 41:1813-1824.
22. Liu Z and Franklin MR (1985) Cytochrome P-450 ligands: metyrapone revisited. Arch Biochem Biophys 241:397-402.
23. Mayhew BS, Jones DR, and Hall SD (2000) An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation. Drug Metab Dispos 28:1031-1037.
24. Miller CD, El-Kholi R, Faragon JJ, and Lodise TP (2007) Prevalence and risk factors for clinically significant drug interactions with antiretroviral therapy. Pharmacotherapy 27:1379-1386.
25. Mizutani T, Yoshida K, and Kawazoe S (1994) Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products. Drug Metab Dispos 22:750-755.
26. Moyle GJ and Back D (2001) Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med 2:105-113.
27. Obach RS, Kalgutkar AS, Ryder TF, and Walker GS (2008) In vitro metabolism and covalent binding of enol-carboxamide derivatives and anti-inflammatory agents sudoxicam and meloxicam: insights into the hepatotoxicity of sudoxicam. Chem Res Toxicol 21:1890-1899.
28. Ortiz de Montellano PR (2005) Cytochrome P450: Structure, Mechanism, and Biochemistry. Kluwer Academic/Plenum Publishers, New York.
29. Ortiz de Montellano PR and Kunze KL (1981) Cytochrome P-450 inactivation: structure of the prosthetic heme adduct with propyne. Biochemistry 20:7266-7271.
30. Racha JK, Rettie AE, and Kunze KL (1998) Mechanism-based inactivation of human cytochrome P450 1A2 by furafylline: detection of a 1:1 adduct to protein and evidence for the formation of a novel imidazomethide intermediate. Biochemistry 37: 7407-7419.
31. Schenkman JB, Wilson BJ, and Cinti DL (1972) Dimethylaminoethyl 2,2-diphenylvalerate HCl (SKF 525-A)-in vivo and in vitro effects of metabolism by rat liver microsomes-formation of an oxygenated complex. Biochem Pharmacol 21:2373-2383.
32. Sevrioukova IF and Poulos TL (2010) Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci USA 107:18422-18427.
33. Shaw PM, Hosea NA, Thompson DV, Lenius JM, and Guengerich FP (1997) Reconstitution premixes for assays using purified recombinant human cytochrome P450, NADPH-cytochrome P450 reductase, and cytochrome b5. Arch Biochem Biophys 348:107-115.
34. Silverman RB (1988) Mechanism-Based Enzyme Inactivation: Chemistry and Enzymology, CRC Press, New York.
35. Subramanian R, Lee MR, Allen JG, Bourbeau MP, Fotsch C, Hong FT, Tadesse S, Yao G, Yuan CC, and Surapaneni S et al. (2010) Cytochrome P450-mediated epoxidation of 2-aminothiazole-based AKT inhibitors: identification of novel GSH adducts and reduction of metabolic activation through structural changes guided by in silico and in vitro screening. Chem Res Toxicol 23:653-663
36. Takakusa H, Wahlin MD, Zhao C, Hanson KL, New LS, Chan EC, and Nelson SD (2011) Metabolic intermediate complex formation of human cytochrome P450 3A4 by lapatinib. Drug Metab Dispos 39:1022-1030.
37. Yates JR, 3rd, Eng JK, McCormack AL, and Schieltz D (1995) Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem 67:1426-1436.