The species-dependent metabolism of Efavirenz produces a nephrotoxic glutathione conjugate in rats

Toxicology and Applied Pharmacology

Volumn 169, Issue 1, 2000, Pages 102-113

  Mutlib, Abdul E ^a   Gerson, Ronald J ^a   Meunier, Paul C ^a   Haley, Patrick J ^a   Chen, Hao ^a   Gan, Lawrence S ^a   Davies, Marc H ^a   Gemzik, Brian ^a   Christ, David D ^a   Krahn, David F ^a   Markwalder, Jay A ^a   Seitz, Steven P ^a   Robertson, Richard T ^a   Miwa, Gerald T ^a  

^a DUPONT COMPANY   (United States)

Author keywords

Efavirenz; Glutathione adduct; Nephrotoxicity; Reactive metabolites

Indexed keywords

ACIVICIN; CYCLOPROPANECARBOXYLIC ACID DERIVATIVE; DEUTERIUM; DRUG METABOLITE; EFAVIRENZ; GAMMA GLUTAMYLTRANSFERASE; GLUTATHIONE; GLUTATHIONE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFECT; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG URINE LEVEL; ENZYME INHIBITION; GLUTATHIONE METABOLISM; HISTOPATHOLOGY; KIDNEY TUBULE EPITHELIUM; KIDNEY TUBULE NECROSIS; MALE; MORBIDITY; NEPHROTOXICITY; NONHUMAN; RAT; SPECIES DIFFERENCE;

ANIMALIA; MACACA FASCICULARIS;

EID: 0034669056     PISSN: 0041008X     EISSN: None     Source Type: Journal    
DOI: 10.1006/taap.2000.9055     Document Type: Article

References (52)

1. Biosynthesis and biotransformation of glutathione S-conjugates to toxic metabolites
2. The acetylation of S-alkylcysteines by the rat
3. Nephrotoxicity of chloroform: Metabolism to phosgene by the mouse kidney
4. The novel non-nucleoside reverse transcriptase inhibitor DMP 266 produces autoinduction of metabolism in rats and rhesus monkeys
5. Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Role in bioactivation and detoxification mechanisms of xenobiotics
6. Characterization and physiological function of rat renal γ-glutamyltranspeptidase
7. Direct enzymatic assay for reduced and oxidized glutathione
8. Thioacylating intermediates as metabolites of S-(1, 2-dichlorovinyl)-L-cysteine and S-(1, 2, 2-trichlorovinyl)-L-cysteine formed by cysteine conjugate β-lyase
9. Bioactivation mechanism of the cytotoxic and nephrotoxic S-conjugate S-(2-chloro-1, 1, 2-trifluoroethyl)-L-cysteine
10. Nephrotoxicity of S-(chloro-1, 1, 2-trifluoroethyl)-L-cysteine the glutathione and cysteine conjugates of chlorotrifluoroethene
11. Mechanism of S-(1, 2-dichlorovinyl)-glutathione induced nephrotoxicity
12. Species-specific nephrotoxicity induced by glutathione conjugation of efavirenz in rats
13. Glutathione S-transferases: The first enzymatic step in mercapturic acid formation
14. The formation and biotransformation of cysteine conjugates of halogenated ethylenes by rabbit renal tubules
15. Viral dynamics of HIV: Implications for drug development and therapeutic strategies
16. Glutathione-degrading capacities of liver and kidney in different species
17. Role of dehydropeptidase-1 in the metabolism of glutathione and its conjugates in the rat kidney
18. Intramolecular determination of primary kinetic isotope effects in hydroxylation catalyzed by cytochrome P-450
19. Nephrotoxicity of the 1:1 acrolein glutathione adduct in the rat
20. Sex and species differences in glutathione S-transferase activities
21. Detoxification reactions of glutathione and glutathione transferases
22. Bioactivation of xenobiotics by formation of toxic glutathione conjugates
23. Bioactivation and cytotoxicity of amino acid and glutathione S-conjugates
24. S-(2-chloroacetyl)-glutathione a reactive glutathione thiol ester and a putative metabolite of 1, 1-dichloroethylene
25. Protein measurement with the Folin phenol reagent
26. 5-Ethyl-5-phenylhydantoin N-glucuronide the major urinary metabolite of 5-ethyl-5-phenylhydantoin (Nirvanol) in the dogs
27. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: Correlation between structural data and enzymatic properties
28. Glutathione transferases: Structure and catalytic activity
29. The interorgan metabolism of glutathione (1980)
30. Kinetic isotope effects in cytochrome P-450 catalyzed oxidation reactions. Intermolecular and Intramolecular deuterium isotope effects during the N-demethylation of N, N-dimethylphenterraine
31. Bucolome N-glucuronide: Purification and identification of a major metabolite of bucolome in rat bile
32. Glutathione conjugates of 2-bromohydroquinone are nephrotoxic
33. Isolation and characterization of carbinolamide and phenolic glucuronide conjugates of (±)-N-methyl-N-(1-methyl-3, 3-diphenylpropyl)formamide and N-formylamphetamine by FAB/MS LC/MS/MS and NMR
34. LC/MS and high field NMR characterization of novel mixed diconjugates of the non-nucleoside HIV-1 reverse transcriptase inhibitor efavirenz
35. Identification and characterization of efavirenz metabolites by LC/MS and high field NMR. Species differences in the metabolism of efavirenz
36. Synthesis and identification of the N-glucuronides of norgallopamil and norverapamil unusual metabolites of Gallopamil and Verapamil
37. The metabolism and disposition of hexachloro-1:3-butadiene in the rat and its relevance to nephrotoxicity
38. Glutathione-dependent biosynthesis and bioactivation of S-(1, 2-dichlorovinyl)-L-cysteine the glutathione and cysteine S-conjugate of the neurotoxin dichloroacetylene in rat tissues and subcellular fractions
39. Practical asymmetric synthesis of efavirenz (DMP 266) an HIV-1 reverse transcriptase inhibitor
40. Determination of toxic pathways of metabolism by deuterium substitution
41. Reactivity of cysteine conjugate sulfoxides: Formation of s-[1-chloro-2-(s-glutathionyl)vinyl]-L-cysteine sulfoxide by reaction of s-(1, 2-dichlorovinyl)-L-cysteine sulfoxide with glutathione
42. Regulation of testosterone hydroxylation by rat liver microsomal cytochrome P450
43. A phase III multicenter randomized open label study to compare the antiretroviral activity and tolerability of efavirenz (EFV) + Indinavir (IDV) versus EFV + zidovudine (ZDV) [Study DMP 266-006]
44. Immunohistochemical localization of α-class and π-class glutathione transferases in normal human tissues
45. Metabolism of N-methylformamide in mice: Primary kinetic deuterium isotope effect and identification of S-(N-methylcarbamoyl) glutathione as a metabolite
46. Enzymic transformation of mercapturic acids derived from halohenated alkenes to reactive and mutagenic intermediates
47. Active site-directed irreversible inhibition of glutathione S-transferases by the glutathione conjugate of tetrachloro-1, 4-benzoquinone
48. The glutathione conjugates of tert-butyl hydroquinone as potent redox cycling agents and possible reactive agents underlying the toxicity of butylated hydroxyanisole
49. Deuterium isotope effect on the metabolism and toxicity of 1, 2-dibromomethane