Pharmacokinetics, metabolism, and routes of excretion of intravenous irofulven in patients with advanced solid tumors

Drug Metabolism and Disposition

Volumn 34, Issue 11, 2006, Pages 1918-1926

  Paci, Angelo ^a   Rezai, Keyvan ^b   Deroussent, Alain ^a   De Valeriola, Dominique ^c   Re, Micheline ^a   Weill, Sophie ^b   Cvitkovic, Esteban ^d   Kahatt, Carmen ^d   Shah, Ajit ^e   Waters, Stephen ^e   Weems, Gary ^e   Vassal, Gilles ^a   Lokiec, François ^b  

^a INSTITUT GUSTAVE ROUSSY   (France)

^b CENTRE RENÉ HUGUENIN   (France)

^c JULES BORDET INSTITUTE   (Belgium)

^d Cvitkovic and Cvitkovic   (France)

^e GUILFORD PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 HYDROXYMETHYLACYLFULVENE; ANTINEOPLASTIC AGENT; CARBON 14; CYCLOPROPANE; DRUG METABOLITE; GLUCURONIDE; GLUTATHIONE; IROFULVEN; UNCLASSIFIED DRUG;

ADVANCED CANCER; AREA UNDER THE CURVE; ARTICLE; CASE REPORT; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONJUGATION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXCRETION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; DRUG TRANSFORMATION; DRUG URINE LEVEL; ELECTROSPRAY MASS SPECTROMETRY; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MALE; MAXIMUM ALLOWABLE CONCENTRATION; PRIORITY JOURNAL; SOLID TUMOR; ULTRAVIOLET SPECTROSCOPY; URINARY EXCRETION;

ANTINEOPLASTIC AGENTS, ALKYLATING; CARBON RADIOISOTOPES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FECES; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MOLECULAR STRUCTURE; NEOPLASMS; SESQUITERPENES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TISSUE DISTRIBUTION;

EID: 33751088563     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.106.010512     Document Type: Article

References (15)

1. Alexandre J, Raymond E, Kaci MO, Brain EC, Lokiec F, Kahatt C, Faivre S, Yovine A, Goldwasser F, Smith SL, et al. (2004) Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients. Clin Cancer Res 10:3377-3385.
2. Dick RA, Yu X, and Kensler TW (2004) NADPH alkenal/one oxidoreductase activity determines sensitivity of cancer cells to the chemotherapeutic alkylating agent irofulven. Clin Cancer Res 10:1492-1499.
3. Eckhardt SG, Baker SD, Britten CD, Hidalgo M, Siu L, Hammond LA, Villalona-Calero MA, Felton S, Drengler R, Kuhn JG, et al. (2000) Phase I and pharmacokinetic study of irofulven, a novel mushroom-derived cytotoxin, administered for five consecutive days every four weeks in patients with advanced solid malignancies. J Clin Oncol 18:4086-4097.
4. Kelner MJ, McMorris TC, Beck WT, Zamora JM, and Taetle R (1987) Preclinical evaluation of illudins as anticancer agents. Cancer Res 47:3186-3189.
5. McMorris TC (1999) Discovery and development of sesquiterpenoid derived hydroxymethylacylfulvene: a new anticancer drug. Bioorg Med Chem 7:881-886.
6. McMorris TC and Anchel M (1965) Fungal metabolites. The structures of the novel sesquiterpenoids illudin-S and -M. J Am Chem Soc 87:1594-1600.
7. McMorris TC, Elayadi AN, Yu J, Hu Y, and Kelner MJ (1999) Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol. Drug Metab Dispos 27:983-985.
8. McMorris TC, Kelner MJ, Wang W, Yu J, Estes LA, and Taetle R (1996) (Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor properties. J Nat Prod 59:896-899.
9. McMorris TC, Staake MD, and Kelner MJ (2004) Synthesis and biological activity of enantiomers of antitumor irofulven. J Org Chem 69:619-623.
10. McMorris TC, Yu J, Lira R, Dawe R, McDonald JR, Waters SJ, Estes LA, and Kelner MJ (2001) Structure-activity studies of antitumor agent irofulven (Hydroxymethylacylfulvene) and analogues. J Org Chem 66:6158-6163.
11. McMorris TC, Yu J, Ngo HT, Wang H, and Kelner MJ (2000) Preparation and biological activity of amino acid and peptide conjugates of antitumor hydroxymethylacylfulvene. J Med Chem 43:3577-3580.
12. Poindessous V, Koeppel F, Raymond E, Comisso M, Waters SJ, and Larsen AK (2003) Marked activity of irofulven toward human carcinoma cells: comparison with cisplatin and ecteinascidin. Clin Cancer Res 9:2817-2825.
13. Tanaka K, Inoue T, Kanai M, and Kikuchi T (1994) Metabolism of illudin S, a toxic substance of Lampteromyces japonicus. IV. Urinary excretion of an illudin S metabolite in rat. Xenobiotica 24:1237-1243.
14. Toda HIA, Tagawa M, Matsunaga Y, Toide K, Teruchi Y, and Fujii T (1998) Identification of the metabolites MGI-114 in rat plasma. Report No PR-114-22-11 MGI Pharma Inc.
15. Urien S, Alexandre J, Raymond E, Brain E, Smith S, Shah A, Cvitkovic E, and Lokiec F (2003) Phase I population pharmacokinetics of irofulven. Anticancer Drugs 14:353-358.