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Titolo:
TOXICOLOGICAL PROFILE AND PHARMACOKINETICS OF A UNILAMELLAR LIPOSOMALVESICLE FORMULATION OF AMPHOTERICIN-B IN RATS
Autore:
BOSWELL GW; BEKERSKY I; BUELL D; HILES R; WALSH TJ;
Indirizzi:
FUJISAWA USA INC,3 PKWY N DEERFIELD IL 60015 NCI BETHESDA MD 20892
Titolo Testata:
Antimicrobial agents and chemotherapy
fascicolo: 2, volume: 42, anno: 1998,
pagine: 263 - 268
SICI:
0066-4804(1998)42:2<263:TPAPOA>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
PULMONARY ASPERGILLOSIS; LIPID FORMULATIONS; CANDIDA-ALBICANS; AMBISOME; RABBITS; INFECTION; SAFETY; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
G.W. Boswell et al., "TOXICOLOGICAL PROFILE AND PHARMACOKINETICS OF A UNILAMELLAR LIPOSOMALVESICLE FORMULATION OF AMPHOTERICIN-B IN RATS", Antimicrobial agents and chemotherapy, 42(2), 1998, pp. 263-268

Abstract

AmBisome (ABLP) is a unilamellar liposomal preparation of amphotericin B that has demonstrated an improved safety profile compared to conventional amphotericin B. Single-and multiple-dose pharmacokinetics weredetermined by using noncompartmental methods for rats administered ABLP at 1, 3, 9, and 20 mg/kg/day. The toxicological profile was evaluated following 30 consecutive days of intravenous ABLP administration. Mean plasma amphotericin B concentrations reached 500 and 380 mu g/ml (males and females, respectively) following 30 days of ABLP administration at 20 mg/kg. The overall apparent half-life was 11.2 +/- 4.5 h (males) or 8.7 +/- 2.2 h (females), and the overall clearance (CL) was 9.4 +/- 5.5 ml/h/kg (males) or 10.2 +/- 4.1 m/h/kg (females), ABLP appears to undergo saturable disposition, resulting in a non-dose-proportional amphotericin B area under the curve and a lower CL at higher doses. Histopathological examination revealed dose-related transitional-cell hyperplasia in the transitional epithelium of the urinary tract (kidney, ureters, and urinary bladder) and moderate hepatocellular necrosis at the 20-mg/kg/day dose, Administration of ABLP in doses of up to 20 mg/kg/day resulted in 100-fold higher plasma amphotericin B concentrations, with significantly lower toxicity than that reported with conventional amphotericin B therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 23:50:17