Author(s):
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Burger, D.M.
;
Hugen, P.W.H.
;
Aarnoutse, R.E.
; Dieleman, J.P.; Prins, J.M.; Poll, T. van der; Veen, J.H. ten; Mulder, J.W.; Meenhorst, P.L.;
Blok, W.L.
; Meer, J.T. van der; Reiss, P.; Lange, J.M.A.
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Subject:
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The role of cytokines in the pathophysiology of febrile illnesses and in host defense against infections Rational Use of Drugs and Pharmaco-epidemiology De rol van cytokinen in de pathofysiologie van koortsende ziekten en in de afweer tegen infecties Rationeel Geneesmiddelengebruik en Farmaco-epidemiologie |
Organization:
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Clinical Pharmacy Internal Medicine |
Journal title:
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Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
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Abstract:
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OBJECTIVE: To describe the pharmacokinetics, safety, and efficacy of twice-daily indinavir + ritonavir regimens DESIGN: A cohort-based survey of HIV-infected patients who either used indinavir 800 mg + ritonavir 100 mg twice daily or indinavir 400 mg + ritonavir 400 mg twice daily. METHODS: Data were extracted from a database of samples sent to our laboratory for measurement of indinavir + ritonavir plasma concentrations. Patient characteristics, safety, and efficacy measurements were collected by retrospective chart review. RESULTS: 100 Patients using 800-mg indinavir + 100-mg ritonavir twice daily and 32 patients using 400-mg indinavir + 400-mg ritonavir twice daily were eligible. Median peak and trough concentrations of indinavir were 6.8 and 0.77 mg/L in the 800/100 group and 2.6 and 0.45 mg/L in the 400/400 group. The most frequently found side effects were nausea and vomiting, which occurred in 22.1% and 34.9% of the patients in the 800/100 and the 400/400 groups, respectively. Viral load data were analyzed for patients who switched from 800-mg indinavir three times daily to one of the indinavir + ritonavir twice daily regimens. At the time of switch 63% (800/100 group) and 60% (400/400 group) had an undetectable viral load and this increased to 77% and 70%, respectively, during follow-up. Patients who switched to the 400/400 group discontinued treatment more frequently than patients who switched to the 800/100 group (70% vs. 26%, p =.008). CONCLUSIONS: Indinavir + ritonavir regimens show improved pharmacokinetic properties, allowing twice-daily dosing with food. Clinical data suggest that safety and efficacy is at least as good as with indinavir three-times-daily regimens without ritonavir. Prospective, comparative trials are needed to properly assess the role in HIV therapy of these twice-daily indinavir + ritonavir regimens.
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