Pharmacological Basis for Concentration-Controlled Therapy with Zidovudine, Lamivudine, and Indinavir [Kakuda TN, et al. AAC 2001;45:236]: The authors studied the variability in plasma concentrations of antiretroviral drugs in 24 treatment-naive patients who were randomized to receive standard therapy or concentration-controlled therapy. For the latter group, the target concentrations were a mean steady-state concentration of 0.19 mg/L for AZT and 0.44 mg/L for 3TC, and a trough concentration of 0.15 mg/L for IDV. Levels were measured at week two, and dose adjustments were made at week four. Among 11 in the concentration-controlled arm, 10 required dose adjustments. The major change was for indinavir, which was adjusted in 9 of the 11 from 800 mg q8h to 600 mg q6h (n = 2), 800 mg q6h (n = 4), or 1,000 mg q8h (n = 3). Analysis of levels at 28 weeks showed further dose adjustments were necessary in only one patient.
Comment: The most important message from this paper seems to be either that the standard dose of indinavir is too low for many patients or else the target trough level selected by the investigators is too high. Most clinicians do not have access to laboratory facilities that can do the concentration-controlled assays that were utilized in this study. Indeed, this is probably not necessary in the era when dual PI therapy is relatively customary, particularly with indinavir-containing regimens.
posted 1/18/2001

back to news table of contents