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Titolo:
PYRAZINE DIAZOHYDROXIDE (NSC-361456) - PHASE-I CLINICAL AND PHARMACOKINETIC STUDIES
Autore:
DHODAPKAR MV; RICHARDSON RL; REID JM; AMES MM;
Indirizzi:
MAYO CLIN & MAYO FDN,DIV MED ONCOL,E-12,200 1ST ST SW ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DIV MED ONCOL ROCHESTER MN 55905
Titolo Testata:
Investigational new drugs
fascicolo: 3, volume: 12, anno: 1994,
pagine: 207 - 216
SICI:
0167-6997(1994)12:3<207:PD(-PC>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
SODIUM-SALT; INVITRO; INVIVO;
Keywords:
PYRAZINE DIAZOHYDROXIDE; PHASE I TRIAL; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
M.V. Dhodapkar et al., "PYRAZINE DIAZOHYDROXIDE (NSC-361456) - PHASE-I CLINICAL AND PHARMACOKINETIC STUDIES", Investigational new drugs, 12(3), 1994, pp. 207-216

Abstract

Pyrazine diazohydroxide (NSC-361456) was identified as an active congener of pyridine 2-diazohydroxide with enhanced stability under physiologic conditions. In this phase I study, 35 patients with advanced cancer received 62 courses of PZDH administered intravenously every 3 weeks at doses ranging from 15-608 mg/m(2). The dose-limiting toxicity was myelosuppression and the maximal tolerated dose was 487 mg/m(2). Hematologic toxicity was delayed and prolonged with median time to recovery about 5 weeks. Mild gastrointestinal toxicity in the form of nauseaand vomiting was fairly common. Ondansetron was effective in reducingnausea and vomiting at higher dose levels. Other less common reactions included stomatitis, diarrhea, fatigue, alopecia, and mild abnormalities of renal function and hepatic enzymes. PZDH pharmacokinetics werecharacterized in 16 patients who received doses of 100-608 mg/m(2). Plasma elimination was fit to one (12/16) or two (4/16) compartment model with a mean k(10) half-life of 11.5 min. Clearance was dose dependent. Hematologic toxicity was related to PZDH dose, AUC and peak plasmaconcentration. The sigmoidal relationships between hematologic toxicity and AUC or peak plasma concentration were well described by the Hill equation. There were no objective responses observed in this study. Based on this study, the recommended dose for phase II evaluation of PZDH using this schedule is 390 mg/m(2).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 21:22:59