RESUMEN
PURPOSE: The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated. METHODS: Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. RESULTS: The coadministration of 20 or 40 mg of omeprazole with indinavir significantly reduced the mean indinavir area under the concentration-versus-time curve (AUC) from 30.0 mg x hr/L (95% confidence interval [CI], 21.9-41.1 mg x hr/L) to 19.7 mg x hr/L (95% CI, 14.6-26.8 mg x hr/L) or 16.0 mg x hr/L (95% CI, 11.8-21.7 mg x hr/L), respectively (p < 0.002). The addition of 200 mg of ritonavir to 800 mg of indinavir in combination with 40 mg of omeprazole significantly increased the mean indinavir AUC from 30.0 mg x hr/L (95% CI, 21.9-41.1 mg x hr/L) to 46.6 mg x hr/L (95% CI, 34.0-63.8 mg x hr/L), but it did not significantly affect mean omeprazole concentrations (p < or = 0.02). CONCLUSION: The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.
Asunto(s)
Antiulcerosos/farmacología , Inhibidores de la Proteasa del VIH/farmacocinética , Indinavir/farmacocinética , Omeprazol/farmacología , Ritonavir/farmacología , Adolescente , Adulto , Antiulcerosos/administración & dosificación , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Inhibidores de la Proteasa del VIH/farmacología , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificaciónRESUMEN
This retrospective cohort study conducted at the Durham Veterans Affairs Medical Center evaluated the effectiveness and safety of lipid-lowering therapy (LLT) in a HIV-infected population as compared with a general population with hyperlipidaemia. Fifty-three HIV-infected subjects who developed dyslipidaemia and 53 age-matched non-HIV-infected subjects receiving LLT were selected. Efficacy of LLT was assessed after three and six months. Non-HIV-infected subjects were more likely to achieve total cholesterol (TC) goals at three and six months (P = 0.045, P = 0.005) and triglyceride (TG) goals at six months (P = 0.017). Less than 45% of HIV-infected subjects met National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) goals at three or six months. While non-HIV-infected subjects were more likely to achieve TC and TG goals than HIV-infected subjects, overall achievement of NCEP III goals was poor. This result was likely due to treatment with inappropriately low doses of statins.