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Titolo:
PHARMACOKINETICS OF NETIVUDINE, A POTENT ANTI-VARICELLA ZOSTER VIRUS DRUG, IN PATIENTS WITH RENAL IMPAIRMENT
Autore:
FILLASTRE JP; GODIN M; LEGALLICIER B; CHRETIEN P; BIDAULT R; GILLOTIN C; WOOTON R; POSNER J; PECK RW;
Indirizzi:
CHU ROUEN,HOP BOIS GUILLAUME F-76031 ROUEN FRANCE UNIV ROUEN,DEPT NEPHROL ROUEN FRANCE CEMAX LAB ROUEN FRANCE WELLCOME RES LABS BECKENHAM BR3 3BS KENT ENGLAND LABS WELLCOME F-92442 ISSY MOULINEAUX FRANCE
Titolo Testata:
Journal of antimicrobial chemotherapy
fascicolo: 5, volume: 37, anno: 1996,
pagine: 965 - 974
SICI:
0305-7453(1996)37:5<965:PONAPA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
7
Recensione:
Indirizzi per estratti:
Citazione:
J.P. Fillastre et al., "PHARMACOKINETICS OF NETIVUDINE, A POTENT ANTI-VARICELLA ZOSTER VIRUS DRUG, IN PATIENTS WITH RENAL IMPAIRMENT", Journal of antimicrobial chemotherapy, 37(5), 1996, pp. 965-974

Abstract

The pharmacokinetics of a single oral 200 mg dose of netivudine 1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development for use in varicella tester virus infections, were studied in 12 renal failure (RF) subjects (creatinine clearance 15 +/- 7 ml/min) and 12 age-matched healthy subjects with normal creatinine clearance. Blood and urine samples were collected up to nine days after drug administration. Concentrations of netivudine and of its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were determined by a specific high performance liquid chromatography assay. The meanpeak plasma concentrations of netivudine, T-max, and volume of distribution were not significantly affected by RF. The elimination half-life of netivudine was approximately 15 h in subjects with normal renal function and 60 h in RF patients. Plasma and renal clearances of netivudine were significantly reduced in RF patients and AUC was three to four times higher in these patients. C-max and AUC of 5 PU were higher in RF patients, and the half-life was also significantly longer. However, the half-life of this metabolite was much lower than that of the parent compound. T-max and the lag time were similar in the two groups. There were highly significant correlations for netivudine and 5 PU between half-life and creatinine clearance and between renal clearance and creatinine clearance. These findings suggest that netivudine dosage may need to be reduced in patients with severe renal failure, and confirm that formation of the 5 PU is independent of the elimination of netivudine from plasma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 09:54:40