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Titolo:
Variable correlation between 6-mercaptopurine metabolites in erythrocytes and hematologic toxicity: Implications for drug monitoring in children withacute lymphoblastic leukemia
Autore:
Innocenti, F; Danesi, R; Favre, C; Nardi, M; Menconi, MC; Di Paolo, A; Bocci, G; Fogli, S; Barbara, C; Barachini, S; Casazza, G; Macchia, P; Del Tacca, M;
Indirizzi:
Univ Pisa, Dept Oncol, Div Pharmacol & Chemotherapy, I-56126 Pisa, Italy Univ Pisa Pisa Italy I-56126 armacol & Chemotherapy, I-56126 Pisa, Italy Univ Pisa, Dept Reprod Med & Dev, I-56126 Pisa, Italy Univ Pisa Pisa Italy I-56126 Dept Reprod Med & Dev, I-56126 Pisa, Italy
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 4, volume: 22, anno: 2000,
pagine: 375 - 382
SICI:
0163-4356(200008)22:4<375:VCB6MI>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE LYMPHOCYTIC-LEUKEMIA; RED-BLOOD-CELLS; MERCAPTOPURINE METABOLITES; CLINICAL PHARMACOKINETICS; 6-THIOGUANINE NUCLEOTIDE; MAINTENANCE CHEMOTHERAPY; ANTICANCER DRUGS; RISK; PHARMACODYNAMICS; PHARMACOLOGY;
Keywords:
6-MP; 6-TGN; metabolism; acute lymphoblastic leukemia; drug monitoring;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Del Tacca, M Univ Pisa, Dept Oncol, Div Pharmacol & Chemotherapy, Via Roma55, I-56126 Pisa, Italy Univ Pisa Via Roma 55 Pisa Italy I-56126 I-56126 Pisa, Italy
Citazione:
F. Innocenti et al., "Variable correlation between 6-mercaptopurine metabolites in erythrocytes and hematologic toxicity: Implications for drug monitoring in children withacute lymphoblastic leukemia", THER DRUG M, 22(4), 2000, pp. 375-382

Abstract

Nineteen pediatric patients affected by acute lymphoblastic leukemia (ALL)were examined weekly with respect to 6-mercaptopurine nucleotide (6-MPN) and 6-thioguanine nucleotide (6-TGN) levels in erythrocytes during the course of maintenance treatment with 6-MP 50 mg/m(2) pel d and results were related to various parameters of bone marrow function to assess, in the same individual, the level of reliability of 6-MP metabolites in predicting a later change in peripheral blood cell counts. Median values for 6-MPN and 6-TGNwere 57 and 200 pmol/8 x 10(8) erythrocytes, respectively, as measured by reversed-phase high-performance liquid chromatography (HPLC). 6-TGN levels in erythrocytes were inversely related with white blood cell count (r = -0.463, p < 0.0001, n = 361), absolute neutrophil count (r = -0.386, p < 0.0001, n = 347), erythrocyte (r = -0.354, p < 0.0001, n = 287), and platelet counts (r = -0.24, p < 0.0001, n = 319) in the majority of patients (n = 10-12), while no correlation was found for 6-MPN. In the remaining children, noevidence of correlation was demonstrated between 6-TGN levels and myelotoxicity. The results confirm the role of 6-TGN as the reference cytotoxic metabolite for evaluating the exposure to 6-MP and identifying treatment compliance in ALL children but indicate the limits of a follow-up based solely on metabolite levels and suggest that a more correct approach remains the double monitoring of 6-TGN and blood cell count with differential.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:35:23