Pharmacokinetics and tolerability of ABX464, a novel first-in-class compound to treat HIV infection, in healthy HIV-uninfected subjects.
J Antimicrob Chemother
; 72(3): 820-828, 2017 03 01.
Article
em En
| MEDLINE
| ID: mdl-27999038
ABSTRACT
Background:
An anti-HIV compound (ABX464) has been developed with a novel mechanism of activity in that it blocks viral gene expression in cells that are already infected.Objectives:
A first-in-man study was conducted to determine the pharmacokinetic and safety profiles of ABX464. This was carried out as an open label, parallel group, single ascending dose, exploratory study.Methods:
Twenty-four male subjects in good health without HIV infection, aged from 18 to 55 years old, with BMIs of 18-27 kg/m 2 were included. A single oral dose of ABX464 (50, 100, 150 or 200 mg) was administered on the morning of day 0 after overnight fasting, with follow-up for 45 days. Safety assessments consisted of vital signs, electrocardiogram, physical examination, laboratory tests and urinalysis. Pharmacokinetic parameters were calculated for ABX464 and its main metabolite ABX-464- N -glucuronide (ABX464-NGlc). The study was registered at https//www.clinicaltrials (trial number NCT02792686).Results:
ABX464 was well tolerated; the most frequent related treatment-emergent adverse events were headaches, nausea and vomiting; they were not considered as treatment-limiting effects. ABX464's C max was observed approximately 2 h after administration in all groups. ABX464 was rapidly and substantially metabolized into ABX464-NGlc. The C max of ABX464-NGlc was observed approximately 4 h post-dose and was about 160-fold higher than that of the parent with a much longer t 1/2 (90-110 h). The ratio of metabolite to parent drug was consistent across the complete dose range.Conclusions:
These studies confirmed that ABX464 is well tolerated and rapidly and substantially metabolized into ABX464-NGlc in human subjects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Fármacos Anti-HIV
Limite:
Adolescent
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Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França