Identification and reactivity of the major metabolite (β-1-glucuronide) of the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in humans

Xenobiotica

Volumn 31, Issue 5, 2001, Pages 277-293

  Zhou, S F ^a   Paxton, J W ^a   Tingle, M D ^a   Kestell, P ^a   Jameson, M B ^a   Thompson, P I ^a   Baguley, B C ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

5,6 DIMETHYLXANTHENONE 4 ACETIC ACID; 6 HYDROXYMETHYL 5 METHYLXANTHENONE 4 ACETIC ACID; GLUCURONIDE; PLASMA PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; COVALENT BOND; DRUG BLOOD LEVEL; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG HYDROLYSIS; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG URINE LEVEL; HUMAN; MALE; MOLECULAR DYNAMICS; MOLECULAR WEIGHT; NONHUMAN; RABBIT; RAT; REACTION ANALYSIS; SOLID PHASE EXTRACTION;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTICOAGULANTS; ANTINEOPLASTIC AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIAZEPAM; DOSE-RESPONSE RELATIONSHIP, DRUG; GABA MODULATORS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GLUCURONIDASE; GLUCURONIDES; HUMANS; HYDROGEN-ION CONCENTRATION; HYDROLYSIS; MALE; MICE; MICE, INBRED C57BL; MODELS, CHEMICAL; PHENYLBUTAZONE; PROTEIN BINDING; RABBITS; RATS; RATS, WISTAR; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TIME FACTORS; WARFARIN; XANTHENES; XANTHONES;

ANIMALIA; ORYCTOLAGUS CUNICULUS;

EID: 0034947850     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.1080/00498250110043544     Document Type: Article

References (42)

1. Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: Relation to vascular effects
2. Predictability of the covalent binding of acidic drugs in man
3. Stereoselective binding properties of naproxen glucuronide diastereomers to proteins
4. The structure and function of the UDP-glucuronosyltransferase gene family
5. Evidence for covalent binding of acyl glucuronides to serum albumin via an amine mechanism as revealed by tandem mass spectrometry
6. Reactivity of tolmetin glucuronide with human serum albumin - Identification of binding sites and mechanisms of reaction by tandem mass spectrometry
7. Determination of serum albumin
8. Net glucuronidation in different rat strains: Importance of microsomal beta-glucuronidase
9. Disposition and chemical stability of telmisartan 1-O-acylglucuronide
10. Properties of acyl glucuronide: Implications for studies of the pharmacokinetics and metabolism of acidic drugs
11. Acyl glucuronide as chemical reactive intermediates
12. Phase I pharmacokinetic and pharmacodynamic study of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent
13. Plasma disposition, metabolism and excretion of the experimental antitumour agent 5,6-dimethylxanthenone-4-acetic acid in the mouse, rat and rabbit
14. In vitro and in vivo irreversible plasma protein binding of beclobric acid enantiomers
15. Covalent binding of diflunisal and probenecid to plasma protein in humans: Persistence of the adducts in the circulation
16. A renal mechanism for the clofibric acid-probenecid interaction
17. Preclinical prediction of factors influencing the elimination of 5,6- dimethylxanthenone-4-acetic acid, a new anticancer drug
18. Studies of tolmetin reversible and irreversible binding to proteins via its glucuronide conjugate
19. Induction of tumour necrosis factor-alpha by single and repeated doses of the antitumour agent 5,6-dimethylxanthenone-4-acetic acid
20. The immunological and metabolic basis of drug hypersensitivities
21. Stereoselecive irreversible binding of ketoprofen glucuronides to albumin: Characterization of the site and the mechanism
22. Potential antitumour agents. 58. Synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumour in vivo
23. Light-induced breakdown of flavone acetic acid and xanthenone analogues in solution
24. Interaction of human serum albumin with the electrophilic metabolite 1-O-gemfibrozil-b-D-glucuronide
25. Genotoxicity of acyl glucuronide metabolites formed from clofibric acid and gemfibrozil: A novel role for phase II-mediated bioactivation in the hepatocarcinogenicity of the parent aglycone
26. In vivo covalent binding of clobibric acid to human plasma proteins and rat liver proteins
27. Nonlinear binding of valproic acid (VPA) and E-D2-valproic acid to rat plasma proteins
28. Irreversible binding of zomepirac to plasma protein in vitro and in vivo
29. Covalent binding of zomepirac glucuronide to proteins: Evidence for a Schiff base mechanism
30. Covalent binding of etodolac acyl glucuronide to albumin in vitro
31. Measurement of protein using bicinchoninic acid
32. Acyl glucronide revisited: Is the glucuronidation process a toxification as well as a detoxification mechanism?
33. The role of β-glucuronidase in drug disposition and drug targeting in humans
34. Tumor-dependent increased plasma nitrate concentrations as an indication of the antitumor effect of flavone-8-acetic acid and analogues in mice
35. Acylation of albumin by 1-O-acyl glucuronide
36. Metabolism and elimination of 5,6-dimethylxanthenone-4-acetic acid in the isolated perfused rat liver
37. Deconjugation of bilirubin-IXa glucuronides: A physiologic role of hepatic microsomal β-glucuronidase
38. Modulation of reversible and covalent interaction of diflunisal acyl glucuronide and its isomers with human plasma protein in vitro
39. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations
40. Identification of the human liver cytochrome P450 isozyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5,6-dimethylxanthenone-4-acetic acid
41. Determination of two major metabolites of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid in hepatic microsomal incubations by high-performance liquid chromatography with fluorescence detection
42. Enhanced covalent binding of tolmetin to proteins in humans after multiple dosing