Identification and characterization of N-acetylcysteine conjugates of valproic acid in humans and animals

Drug Metabolism and Disposition

Volumn 28, Issue 7, 2000, Pages 823-832

  Gopaul, Sashi V ^a   Farrell, Kevin ^a   Abbott, Frank S ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

2 PROPYL 4 PENTENOIC ACID; ACETYLCYSTEINE; CYTOCHROME P450; DRUG METABOLITE; EPOXIDE; GLUCURONIDE; GLUTATHIONE; KETONE DERIVATIVE; LACTONE DERIVATIVE; VALPROIC ACID;

ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DECARBOXYLATION; DRUG CONJUGATION; DRUG DETOXIFICATION; DRUG GLUCURONIDATION; DRUG METABOLISM; DRUG TRANSFORMATION; DRUG URINE LEVEL; ENZYME MECHANISM; GUINEA PIG; HUMAN; LIVER TOXICITY; MALE; PRIORITY JOURNAL; RAT;

ACETYLCYSTEINE; ANIMALS; BIOTRANSFORMATION; CHROMATOGRAPHY, LIQUID; ESTERS; GUINEA PIGS; HUMANS; HYDROLYSIS; MASS SPECTROMETRY; RATS; VALPROIC ACID;

ANIMALIA; CAVIA; CAVIA PORCELLUS; SUS SCROFA;

EID: 0033912868     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (33)

1. Abbott FS, Kassam J, Acheampong A, Ferguson S, Panesar SK, Burton R, Farrell K and Orr J (1986) Capillary gas chromatography-mass spectrometry of valproic acid metabolites in serum and urine using tert-butyldimethylsilyl derivatives. J Chromatogr 375:285-298.
2. Acheampong AA, Abbott FS and Burton R (1983) Identification of valproic acid metabolites in human serum and urine using hexadeuterated valproic acid and gas chromatographic mass spectrometric analysis. Biomed Mass Spectrom 10:586-595.
3. Baillie TA (1988) Metabolic activation of valproic acid and drug mediated hepatotoxicity. Role of the terminal olefin, 2-n-propyl-4-pentenoic acid. Chem Res Toxicol 1:195-199.
4. Bjorge SM and Baillie TA (1991) Studies on the β-oxidation of valproic acid in rat liver mitochondrial preparations. Drug Metab Dispos 19:829.
5. Bowden CL, Brugger AM, Swann AC, Calabrese JR, Janicack PG, Petty F, Dilsaver SC, Davis JM, Rush AJ, Small JG, Garza-Trevino ES, Risch SC, Goodnick PJ and Morris DD (1994) Efficacy of divalproex vs. lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA 271:918-924.
6. Bryant AE 3rd and Dreifuss FE (1996) Valproic acid hepatic failures fatalities. III. U.S. experience since 1986. Neurology 46:465-469.
7. Citrome L, Levine J and Allingham B (1998) Utilization of valproate: Extent of inpatient use in the New York State Office of Mental Health. Psychiatr Q 69:283-300.
8. Costello LE and Suppes T (1995) A clinically significant interaction between clozapine and valproate. J Clin Psychopharmacol 15:139-140.
9. Cotariu D, Evans S, Zaidman JL and Marcus O (1990) Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid. Biochem Pharmacol 40:589-593.
10. Gerber N, Dickinson RC, Harland RH, Lyn RK, Houghton D, Antonias JI and Schimschok JC (1979) Reye-like syndrome associated with valproic acid therapy. J Pediatr 95:142-144.
11. Graminski GF, Kubo Y and Armstrong RN (1989) Spectroscopic and kinetic evidence for the thiolate anion of glutathione at the active site of glulathione S-transferase. Biochemistry 28:3562-3568.
12. Granneman GR, Wang SI, Machinist JM and Kesterson JW (1984) Aspects of the metabolism of valproic acid. Xenobiotica 14:375-387.
13. Hinchman CA and Ballatori N (1994) Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process. J Toxicol Environ Health 41:387-409.
14. Kassahun K and Abbott F (1993) In vivo formation of the thiol conjugates of reactive metabolites of 4-ene VPA and its analogue 4-pentenoic acid. Drug Metab Dispos 21:1098-1106.
15. Kassahun K and Baillie T (1993) Cytochrome P-450-mediated dehydrogenation of 2-n-propyl-2-(E)-pentenoic acid, a pharmacologically active metabolite of valproic acid, in rat liver microsomal preparations. Drug Metab Dispos 21:242-248.
16. Kassahun K, Farrell K and Abbott FS (1991) Identification and characterization of the glutathione and N-acetyleysteine conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans. Drug Metab Dispos 21:1098-1106.
17. Kassahun K, Farrell K, Zheng J and Abbott FS (1990) Metabolic profiling of valproic acid in patients using negative ion chemical ionization gas chromatography-mass spectrometry. J Chromatogr 527:327-341.
18. Kassahun K, Hu P, Grillo P, Davis MR, Jin L and Baillie TA (1994) Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and independent processes. Chem Biol Interact 90:253-275.
19. Kesterson JW, Granneman GR and Machinist JM (1984) The hepatotoxcity of valproic acid and its metabolites in rats. I: Toxicologic, biochemical and histopathologic studies. Hepatology 4:1143-1152.
20. Osmundsen H and Hovik R (1988) β-Oxidation of polyunsaturated fatty acids Biochem Soc Trans 16:420-422.
21. Rettenmeier AW, Gordon WP, Barnes H and Baillie TA (1987) Studies on the metabolic fate of valproic acid in the rat using stable isotope techniques. Xenobiotica 17:1147-1157.
22. Rettenmeier AW, Gordon WP, Prickett KS, Levy RH and Baillie TA (1986a) Biotransformation and pharmacokinetics in the rhesus monkey of 2-n-propyl-pentenoic acid, a toxic metabolite of valproic acid. Drug Metab Dispos 14:454-463.
23. Rettenmeier AW, Gordon WP, Prickett KS, Levy RH, Lockard JS, Thummel KE and Baillie TA (1986b) Metabolic fate of valproic acid in the rhesus monkey. Formation of a toxic metabolite. 2-n-propyl-pentenoic acid. Drug Metab Dispos 14:443-453.
24. Rettenmeier AW, Prickett KS, Gordon WP, Bjorge SM, Chang SL, Levy RH and Baillie TA (1985) Studies on the biotransformation in the perfused rat liver of 2-n-propyl-4-pentenoic acid, a metabolite of the antiepileptic drug valproic acid; Evidence for the formation of the chemically reactive intermediates. Drug Metab Dispos 13:81-96.
25. Silverstein RH, Bassler GC and Morrill TC (1981) Spectroscopic Identification of Organic Compounds, 4th ed., pp 181-247. John Wiley and Sons, New York.
26. Swann AC, Bowden CL, Morris D, Calabrese JR, Small J. Petty F. Dilsaver SC and Davis JM (1997) Depression during mania: Treatment response to lithium or divalproex. Arch Gen Psychiatry 54:37-42.
27. Tang W and Abbott FS (1996a) Bioactivation of a toxic metabolite of valproic acid. (E)-2-propyl-2,4-pentadienoic acid, via glucuronidation. LC/MS/MS characterization of the GSH-glucuronide diconjugates. Chem Res Toxicol 9:517-526.
28. Tang W and Abbott FS (1996b) Characterization of thiol conjugated metabolites of 2-propylpent-4-enoic acid (4-ene VPA), a toxic metabolite of valproic acid, by electrospray tandem mass spectrometry. J Mass Spectrom 31:926-936.
29. Tang W, Borel AG and Abbott FS (1996a) Conjugation of glutathione with a toxic metabolite of valproic acid, (E)-2-n-propyl-2,4-pentadienoic acid, catalyzed by rat hepatic glutathione-S-transferases. Drug Metab Dispos 24:436-446.
30. Tang W, Tabatabaei A and Abbott FS (1996b) Differences in the metabolic activation of 4-ene VPA between guinea pigs and rats. ISSX Proc 10:89.
31. Te Koppele JM, Van der Mark EDJ and Mulder GJ (1988) Liquid chromatographic determination of diastereomeric glutathione conjugates and further derivatives of α-bromoisovalerylurea in rat bile and urine by electrochemically generated bromine. J Chromatogr 427:67-77.
32. Te Koppele JM, van der Mark EDJ, Olde Boerrigter JC, Brussee J, van der Gen A, van der Greef J and Mulder GJ (1986) α-Bromoisovalerylurea as model substrate for studies on pharmacokinetics of glutathione conjugation in the rat. I. (Bio-) synthesis, analysis and identification of diastereomeric glutathione and merecapturates. J Pharmacol Exp Ther 239:898-904.
33. Zimmerman HJ and Ishak KG (1982) Valproate-induced hepatic injury: Analyses of 23 fatal cases. Hepatology 2:591-597.