Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir

Adriana S A Andrade, Craig Hendrix, Teresa L Parsons, Benjamin Caballero, Chun-Su Yuan, Charles W Flexner, Adrian S Dobs, Todd T Brown, Adriana S A Andrade, Craig Hendrix, Teresa L Parsons, Benjamin Caballero, Chun-Su Yuan, Charles W Flexner, Adrian S Dobs, Todd T Brown

Abstract

Background: Complementary and alternative medicine (CAM) use is prevalent among HIV-infected patients to reduce the toxicity of antiretroviral therapy. Ginseng has been used for treatment of hyperglycemia and insulin resistance, a common side effect of some HIV-1 protease inhibitors (PI). However, it is unknown whether American ginseng (AG) can reverse insulin resistance induced by the PI indinavir (IDV), and whether these two agents interact pharmacologically. We evaluated potential pharmacokinetic interactions between IDV and AG, and assessed whether AG improves IDV-induced insulin resistance.

Methods: After baseline assessment of insulin sensitivity using the insulin clamp technique, healthy volunteers received IDV 800 mg q8 h for 3 days and then IDV and AG 1g q8h for 14 days. IDV pharmacokinetics and insulin sensitivity were assessed before and after AG co-administration.

Results: There was no difference in the area-under the plasma-concentration-time curve after the co-administration of AG, compared to IDV alone (n = 13). Although insulin-stimulated glucose disposal per unit of insulin (M/I) decreased by an average of 14.8 +/- 5.9% after 3 days of IDV (from 0.113 +/- 0.012 to 0.096 +/- 0.014 mg/kgFFM/min per muU/ml of insulin, p = 0.03, n = 11), M/I remained unchanged after co-administration of IDV and AG.

Conclusion: IDV decreases insulin sensitivity, which is unaltered by AG co-administration. AG does not significantly affect IDV pharmacokinetics.

Figures

Figure 1
Figure 1
Fasting Glucose Concentrations in Leptin-Deficient (ob/ob) Mice Treated with AG-Extract (250 mg/kg) and Vehicle Over 12 Days (n = 6 in both groups).
Figure 2
Figure 2
Insulin Sensitivity (Glucose Infusion Rate Per Kilogram of Free-Fat Mass Per Unit of Insulin) at Baseline, After 3 Days of Indinavir, and After 14 Days of Co-Administration of AG in Healthy Volunteers (p-values represent the average mean difference by paired t-test).

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