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Titolo:
ABSOLUTE BIOAVAILABILITY AND METABOLIC DISPOSITION OF VALACICLOVIR, THE L-VALYL ESTER OF ACYCLOVIR, FOLLOWING ORAL-ADMINISTRATION TO HUMANS
Autore:
SOULLAWTON J; SEABER E; ON N; WOOTTON R; ROLAN P; POSNER J;
Indirizzi:
WELLCOME FDN LTD,DEPT CLIN PHARMACOL BECKENHAM BR3 3BS KENT ENGLAND
Titolo Testata:
Antimicrobial agents and chemotherapy
fascicolo: 12, volume: 39, anno: 1995,
pagine: 2759 - 2764
SICI:
0066-4804(1995)39:12<2759:ABAMDO>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
PREVENTION; DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
13
Recensione:
Indirizzi per estratti:
Citazione:
J. Soullawton et al., "ABSOLUTE BIOAVAILABILITY AND METABOLIC DISPOSITION OF VALACICLOVIR, THE L-VALYL ESTER OF ACYCLOVIR, FOLLOWING ORAL-ADMINISTRATION TO HUMANS", Antimicrobial agents and chemotherapy, 39(12), 1995, pp. 2759-2764

Abstract

Valaciclovir (Valtrex), the L-valyl ester of acyclovir, is undergoingclinical development for the treatment and suppression of herpesviraldiseases. The absolute bioavailability of acyclovir from valaciclovirand the metabolic disposition of valaciclovir were investigated with healthy volunteers in two separate studies. In a randomized, crossoverstudy, 12 fasting healthy volunteers each received 1,000 mg of oral valaciclovir and a 1-h intravenous infusion of 350 mg of acyclovir, Themean absolute bioavailability of acyclovir was 54.2%, a value three to five times that obtained previously with oral acyclovir, A similar estimate of 51.3% was made from urinary recovery of acyclovir. In the second study, four fasting volunteers received a single oral dose of 1,000 mg of [C-14]valaciclovir. The majority of plasma radioactivity wasaccounted for by acyclovir, with very low plasma valaciclovir concentrations (mean maximum concentration of drug in plasma = 0.19 mu M), which were undetectable after 3 h postdose. By 168 h, more than 90% of the administered radioactive dose was recovered, with approximately 46%in urine and 47% in feces, More than 99% of the radioactivity recovered in urine corresponded to acyclovir and its known metabolites, 9-(carboxymethoxymethyl)guanine and 8-hydroxy-9-[(2-hydroxyethoxy)methyl]guanine, with valaciclovir accounting for less than 0.5% of the dose, Acyclovir, but no valaciclovir, was detected in fecal samples, These studies show that after oral administration to humans, valaciclovir is rapidly and virtually completely converted to acyclovir to provide a high level of acyclovir bioavailability in comparison,vith that followingoral administration of acyclovir, The plasma acyclovir exposure obtained following oral administration of valaciclovir is similar to that achieved,vith doses of intravenous acyclovir, which are effective in the treatment and suppression of the less susceptible herpesviral diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 15:54:32