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Titolo:
PHARMACOKINETICS OF 3-METHYL-(TRIAZEN-1-YL)IMIDAZOLE-4-CARBOXIMIDE FOLLOWING ADMINISTRATION OF TEMOZOLOMIDE TO PATIENTS WITH ADVANCED CANCER
Autore:
REID JM; STEVENS DC; RUBIN J; AMES MM;
Indirizzi:
MAYO CLIN & MAYO FDN,DEPT ONCOL ROCHESTER MN 55905
Titolo Testata:
Clinical cancer research
fascicolo: 12, volume: 3, anno: 1997,
parte:, 1
pagine: 2393 - 2398
SICI:
1078-0432(1997)3:12<2393:PO3F>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN TUMOR-CELLS; ANTITUMOR IMIDAZOTETRAZINES; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CYTOTOXICITY; DACARBAZINE; SENSITIVITY; TRIAL; MICE; DRUG; DNA;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
15
Recensione:
Indirizzi per estratti:
Citazione:
J.M. Reid et al., "PHARMACOKINETICS OF 3-METHYL-(TRIAZEN-1-YL)IMIDAZOLE-4-CARBOXIMIDE FOLLOWING ADMINISTRATION OF TEMOZOLOMIDE TO PATIENTS WITH ADVANCED CANCER", Clinical cancer research, 3(12), 1997, pp. 2393-2398

Abstract

The antitumor activity of temozolomide (TMZ) is believed to arise viaformation of the reactive, alkylating metabolite 3-methyl-(triazen-1-yl)imidazole-4-carboximide (MTIC), which is produced by chemical hydrolysis of the parent drug, MTIC has not been quantitated in plasma or urine following administration of TMZ to patients, We developed a sensitive, specific method for the determination of MTIC levels in plasma, based on reverse-phase high-pressure liquid chromatography of the supernatant that is obtained by methanol precipitation of plasma proteins,Due to poor stability under physiological conditions, determination of MTIC required rapid specimen processing, precipitation of plasma proteins with methanol, and storage of the methanolic supernatant at -70 degrees C, The pharmacokinetics of MTIC were studied in 15 patients who received 125-250 mg/m(2) TMZ, Peak plasma concentrations of 0.07-0.61 mu g/ml MTIC were observed approximately 1 h after a p.o. dose of TMZ, Appearance and disappearance (t(1/2), 88 min) of the reactive metabolite paralleled the appearance and disappearance of TMZ in plasma, The mean values of the metabolite peak plasma concentration and AUC were2.6% (range, 1.6-4.6%) and 2.2% (range, 0.8-3.6%), respectively, of the values for TMZ, MTIC did not accumulate in plasma following five consecutive daily doses of TMZ.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 13:25:20