Dose-Finding Study of a Once-Daily Indinavir/Ritonavir Regimen [Hugen PWH, et al. JAIDS 2000;25:236]: This is another dose-finding study in which participants took various doses of the two PIs. The optimal regimen based on pharmacokinetics was 1200 mg indinavir plus 400 mg ritonavir, but it was poorly tolerated. The authors concluded that the initial daily dose should be indinavir 1200 mg plus ritonavir 400 mg. Once the steady state was achieved with ritonavir, the regimen could be changed to indinavir 1200 mg plus ritonavir 200 mg or indinavir 800 mg plus ritonavir 400 mg.
Comment: These two studies examined possible dose regimens for once-daily indinavir plus ritonavir based on pharmacokinetics. One of the major differences between the two was a goal of indinavir concentrations >0.1 ug/mL at 12 hours in the report by Mallolas, et al. versus this level at 24 hours in the report by Hugen, et al. With 100 or 200 mg ritonavir, the level of ritonavir was always below the IC 90 of 2.1 ug/mL indicating that it was not active as an antiretroviral agent. With 100 mg/day there was no detectable trough level of this drug so that indinavir metabolism was not affected. The study by Hugen, et al. concluded that an initial dose of indinavir 1200 mg plus ritonavir 400 mg was necessary to achieve adequate plasma levels initially, but this dose could be subsequently reduced in the maintenance phase. Neither study could address the issue of nephrotoxicity or the impact of this regimen on lipodystrophy.
posted 12/27/2000

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