Effect of faldaprevir on raltegravir pharmacokinetics in healthy volunteers.
J Clin Pharmacol
; 55(4): 384-91, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25352040
ABSTRACT
Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label, 2-period, fixed-sequence study, 24 healthy volunteers (12 males) received faldaprevir 240 mg and raltegravir 400 mg in 2 treatment schedules (A and B) separated by a washout phase of ≥7 days (A) twice-daily raltegravir (Days 1-3), once-daily raltegravir (Day 4); (B) twice-daily raltegravir and twice-daily faldaprevir (loading dose, Day 1), twice-daily raltegravir and once-daily faldaprevir (Days 2-5), once-daily raltegravir and once-daily faldaprevir (Day 6). Pharmacokinetics and safety were assessed over 132 hours post-dosing. Compared with raltegravir alone, co-administration with faldaprevir led to 2.7-fold and 2.5-fold increases in raltegravir geometric mean AUC(τ,ss) and C(max,ss), respectively, and a similar increase in raltegravir glucuronide metabolite exposure. No serious adverse events (AEs) were reported and no subject discontinued due to AEs. Faldaprevir and raltegravir co-administration was well tolerated and resulted in a moderate increase in raltegravir exposure.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
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Inhibidores de Proteasas
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Tiazoles
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Inhibidores de Integrasa VIH
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Raltegravir Potásico
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos