Effect of High-Dose Vitamin C on the Steady-State Pharmacokinetics of the Protease Inhibitor Indinavir in Healthy Volunteers

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 (C_max), time to C_max, area under the plasma concentration–time curve from 0–5 hours after the dose (AUC_0–5), an extrapolated 8-hour AUC (AUC_0–8), trough (minimum) plasma concentration (C_min), and oral clearance. Mean steady-state indinavir C_max 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 AUC_0–8 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 C_min 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.