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1.
Clin Infect Dis ; 48(4): 489-92, 2009 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-19143531

RESUMEN

Raltegravir, a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has pH-dependent solubility. Raltegravir plasma concentration increases with omeprazole coadministration in healthy subjects; this is likely secondary to an increase in bioavailability attributable to increased gastric pH. Increased gastric pH has been reported in HIV-1-infected individuals, and the effects of omeprazole in this intended population may be diminished. Further investigation is necessary.


Asunto(s)
Fármacos Anti-VIH/farmacocinética , Interacciones Farmacológicas , Omeprazol/farmacocinética , Plasma/química , Pirrolidinonas/farmacocinética , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/uso terapéutico , Pirrolidinonas/uso terapéutico , Raltegravir Potásico , Adulto Joven
2.
J Clin Pharmacol ; 54(7): 765-75, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24615657

RESUMEN

Anacetrapib is a cholesteryl ester transfer protein inhibitor in Phase III development. This double-blind, double-dummy, randomized, placebo- and active-comparator-controlled, 4-period, balanced crossover study evaluated the effects of anacetrapib (100 mg and 800 mg) on QTcF interval in healthy subjects. QTcF measurements were made up to 24 h following administration of single doses of anacetrapib 100 or 800 mg, moxifloxacin 400 mg, or placebo in the fed state. The primary hypothesis was supported if the 90% CI for the least squares (LS) mean differences between anacetrapib 800 mg and placebo in QTcF interval change from baseline were entirely <10 msec at every post-dose time point (1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 h). The upper bounds of the 90% CIs for LS mean differences from placebo in changes from baseline in QTcF intervals for anacetrapib 100 and 800 mg were <5 msec at every time point. In conclusion, single doses of anacetrapib 100 and 800 mg do not prolong the QTcF interval to a clinically meaningful degree relative to placebo and are generally well tolerated in healthy subjects.


Asunto(s)
Anticolesterolemiantes/administración & dosificación , Proteínas de Transferencia de Ésteres de Colesterol/antagonistas & inhibidores , Drogas en Investigación/administración & dosificación , Corazón/efectos de los fármacos , Modelos Biológicos , Oxazolidinonas/administración & dosificación , Adolescente , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/sangre , Antibacterianos/farmacocinética , Anticolesterolemiantes/efectos adversos , Anticolesterolemiantes/sangre , Anticolesterolemiantes/farmacocinética , Arritmias Cardíacas/inducido químicamente , Estudios de Cohortes , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Drogas en Investigación/efectos adversos , Drogas en Investigación/farmacocinética , Electrocardiografía/efectos de los fármacos , Femenino , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/sangre , Fluoroquinolonas/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Moxifloxacino , Oxazolidinonas/efectos adversos , Oxazolidinonas/sangre , Oxazolidinonas/farmacocinética , Inhibidores de Topoisomerasa II/administración & dosificación , Inhibidores de Topoisomerasa II/efectos adversos , Inhibidores de Topoisomerasa II/sangre , Inhibidores de Topoisomerasa II/farmacocinética , Adulto Joven
3.
J Clin Pharmacol ; 52(10): 1566-73, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22162542

RESUMEN

In this open-label study, 24 healthy volunteers received a single intravenous (IV) dose of 0.5 mg of midazolam on day 1 and a single oral dose each of 2 mg of midazolam and 0.5 mg of digoxin on day 3. Telaprevir 750 mg every 8 hours was administered from day 8 through day 23, along with a single IV dose of 0.5 mg of midazolam on day 17 and single oral doses of 2 mg of midazolam and 0.5 mg of digoxin on day 19. Midazolam, 1'-hydroxymidazolam, digoxin, and telaprevir concentrations in plasma and digoxin concentrations in urine were measured and pharmacokinetic parameters calculated. On comparing administration with versus without telaprevir, the geometric least squares mean ratios (with 90% confidence limits) for IV midazolam were 1.02 (0.80, 1.31) for maximum observed concentrations (C(max)) and 3.40 (3.04, 3.79) for area under the curve from 0 to 24 hours (AUC(0-24h)); for oral midazolam 2.86 (2.52, 3.25) for C(max) and 8.96 (7.75, 10.35) for AUC(0-24h); and for oral digoxin 1.50 (1.36, 1.65) for C(max) and 1.85 (1.70, 2.00) for area under the curve from 0 to infinity (AUC(0-∞)). Coadministration of telaprevir with oral midazolam resulted in approximately 3-fold decrease in the mean AUC(0-∞) of 1'-hydroxymidazolam. The renal clearance of digoxin was similar with or without telaprevir. Results show that telaprevir is an inhibitor of CYP3A and P-glycoprotein.


Asunto(s)
Antivirales/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A , Digoxina/farmacocinética , Midazolam/farmacocinética , Oligopéptidos/administración & dosificación , Inhibidores de Proteasas/administración & dosificación , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Antivirales/sangre , Antivirales/farmacocinética , Área Bajo la Curva , Citocromo P-450 CYP3A/metabolismo , Digoxina/administración & dosificación , Digoxina/sangre , Digoxina/orina , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Midazolam/administración & dosificación , Midazolam/análogos & derivados , Midazolam/sangre , Persona de Mediana Edad , Oligopéptidos/sangre , Oligopéptidos/farmacocinética , Inhibidores de Proteasas/sangre , Inhibidores de Proteasas/farmacocinética , Adulto Joven
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