• vitamin C;
  • ascorbic acid;
  • indinavir;
  • protease inhibitors;
  • antiretroviral agents;
  • human immunodeficiency virus;
  • pharmacokinetics;
  • CYP3A4

Study Objective. To determine whether daily high-dose vitamin C alters the steady-state pharmacokinetics of indinavir, a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1.

Design. Prospective, open-label, longitudinal, two-period time series.

Setting. University medical center.

Subjects. Seven healthy volunteers.

Intervention. Indinavir 800 mg every 8 hours was given to subjects for four doses on days 1 and 2. Plasma samples were then collected for indinavir pharmacokinetic determination. After a 7-day washout period, subjects were given vitamin C 1000 mg/day for 7 days. Beginning on day 6 of vitamin C administration, indinavir 800 mg every 8 hours was restarted for four doses. Plasma was then collected from subjects to determine indinavir pharmacokinetics. All subjects were given a vitamin C content–controlled diet for 1 week before the study began and throughout the study period.

Measurements and Main Results. Steady-state plasma samples were collected before dosing (0 hr) and 0.5, 1, 2, 3, 4, and 5 hours after dosing to determine indinavir pharmacokinetics. Parameters of interest were maximum plasma concentration (Cmax), time to Cmax, area under the plasma concentration–time curve from 0–5 hours after the dose (AUC0–5), an extrapolated 8-hour AUC (AUC0–8), trough (minimum) plasma concentration (Cmin), and oral clearance. Mean steady-state indinavir Cmax was significantly reduced (20%) after 7 days of vitamin C administration (10.3 ± 1.5 vs 8.2 ± 2.9 μg/ml, p=0.04). The corresponding mean AUC0–8 was also significantly decreased (14%; 26.4 ± 7.2 vs 22.7 ± 8.1 μg·hr/ml, p=0.05). Although not statistically significant, the mean indinavir Cmin was 32% lower in the presence of vitamin C (0.27 ± 0.17 C vs 0.18 ± 0.08 μg/ml, p=0.09). Indinavir oral clearance and half-life were not significantly different.

Conclusion. Concomitant administration of high doses of vitamin C can reduce steady-state indinavir plasma concentrations. Subtherapeutic concentrations of antiretroviral agents have been associated with viral resistance and regimen failure, but the clinical significance of our findings remains to be established.