Vitamin C induces P4503A4 and reduces indinavir levels

Douglas Slain and colleagues from University of West Virginia presented results from a diet-controlled longitudinal study PK study that found an interaction between Vitamin C and indinavir.

Seven HIV-negative volunteers were given four consecutive doses of 800mg indinavir every eight hours and baseline indinavir levels recorded hourly after the fourth dose. Following a washout period, Vitamin C was given at a dose of 1 gram/day for seven days with indinavir administration repeated for the last 36 hours. Dosing of Vitamin C and indinavir was separated by several hours.

Results showed a significant reduction on indinavir levels. Cmax levels were reduced by -20% (p=0.04) and steady state eight-hour AUC by –14% (p<0.05). Cmin levels were 32% lower from 265 ng/mL to 181 ng/mL although this parameter was not statistically significant (p+0.09).

Comment

These reduced levels are easily likely to be overcome in combinations where indinavir is used in regimes where it is boosted by ritonavir, and in practice this accounts for the majority of people still using this protease inhibitor.

However, although this study refers to high-dose Vitamin C, 1g doses are available over-the-counter and probably not unusual in people who believe in benefits of Vitamin supplements (ie in prevention of colds and flu). This interaction on a P4503A4 substrate could be just as important for other medications used in treatment and management of HIV metabolised in the same way.

Slain D, Amsden JR, Khakoo RA et al. 1, Effect of high-dose Vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. 43rd ICAAC, Sep, 2003; Abstract A-1610.