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In the past, indinavir has been dosed three times a day. Indinavir has been used extensively since the advent of highly active antiretroviral therapy HAART and is known to be effective, both in improving the levels of surrogate markers and in extending life in combination with other agents. However, dietary restrictions and three times daily dosing has tempered the attractiveness of indinavir as a treatment for many patients. Low doses of ritonavir can be used to boost serum levels of indinavir by inhibiting cytochrome P 3A4 within the liver, allowing less frequent dosing, therefore improving tolerability. Merck protocol Fig. The renal toxicity of this combination, consisting of loin pain and nephrolithiasis, has varied between studies ; work by the Rockstroh group, as mentioned below and may, in part, be determined by climate more common in hotter areas and certainly by hydration.
Pharmacokinetic enhancement involves the use of one drug to inhibit the metabolism of another, leading to improved drug exposure. Ritonavir increases exposure and slows the metabolism of other protease inhibitors leading to potential for using fewer tablets and having less frequent dosing. It also removes the need for food restrictions and at least with saquinavir the need to separate dosing from buffered ddI. Furthermore, the interpatient variability in exposure with PIs is diminished when ritonavir co-dosing is used. Ritonavir is also known to inhibit p-glycoprotein, a cellular efflux pump.
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The comparison of triple therapy with zidovudine, lamivudine and either mg efavirenz once daily or mg indinavir every 8 hours, for the treatment of human immunodeficiency virus HIV. The study population consisted of HIV-positive people with limited exposure to nucleoside reverse transcriptase inhibitors. The average time since diagnosis was 3.
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