Pharmacokinetics and tolerability of GW420867X, a nonnucleoside reverse transcriptase inhibitor, following single escalating doses in healthy male volunteers.
J Clin Pharmacol
; 41(10): 1098-105, 2001 Oct.
Article
en En
| MEDLINE
| ID: mdl-11583478
ABSTRACT
The aim of the current study was to characterize the pharmacokinetics of GW420867X, a new nonnucleoside reverse transcriptase inhibitor, using a single escalating dose protocol in healthy volunteers. Four dose levels were investigated in sequential order 300, 600, 900, and 1200 mg, with a ratio of 41 subjects receiving active or placebo treatment, respectively. Following single-dose administration, GW420867X was readily absorbed with a median time to peak concentration of 3 to 5 hours. GW420867X plasma exposure (AUC) was dose proportional but variable within the 300 to 1200 mg dose range. Less than dose-proportional increases were observed for Cmax. The terminal elimination t(1/2) was 50 hours, which supports once-daily dosing in future studies. Plasma trough concentrations of GW420867X at 24 hours after dosing were many fold greater than the in vitro IC50 HIV-1(HXB2) in MT4 cells. GW420867X was generally well tolerated following single-dose administration up to 900 mg; increased central nervous system-related adverse events were observed at higher doses. GW420867X had a favorable pharmacokinetic and safety profile that would enable this drug to be explored in future clinical studies with HIV-1 infected patients at doses that would provide appropriate safety and efficacy.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinoxalinas
/
Inhibidores de la Transcriptasa Inversa
Tipo de estudio:
Clinical_trials
/
Guideline
Límite:
Adolescent
/
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos