Effect of Ginkgo Biloba on the Pharmacokinetics of Raltegravir in Healthy Volunteers

Abstract

dMedicinal herbs may cause clinically relevant drug interactions with antiretroviral agents. Ginkgo biloba extract is a popular herbal product among HIV-infected patients because of its positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor, is increasingly being used as part of combined antiretroviral therapy. Clinical data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of raltegravir in an openlabel, randomized, two-period, crossover phase I trial in 18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of ginkgo biloba twice daily for 15 days plus a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of raltegravir on day 36 or the test and reference treatments in reverse order. Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on an empty stomach. All subjects (9 male) completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from dosing to infinity (AUC 0-ؕ ) and the maximum plasma concentration (C max ) of raltegravir with ginkgo biloba versus raltegravir alone were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The potential increase in the C max of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.

Quantitative prediction and clinical evaluation of an unexplored herb–drug interaction mechanism in healthy volunteers

“…In general, the proof-of-concept clinical study suggested a low interaction risk of silibinin administered with raloxifene. These data are consistent with evaluation of herbal products as inhibitors of hepatic glucuronidation in healthy volunteers [43][44][45][46][47] and support the assertion that drug interaction risk for UGT substrates is generally low. 48 However, multiple subjects demonstrated nearly 2-fold increases in raloxifene exposure, suggesting that the interaction potential should not be disregarded entirely.…”

Herbal Bioenhancers in Veterinary Phytomedicine

“…G. biloba exerting a significant inductive effect on CYP2C19, were found to induce omeprazole hydroxylation in a CYP2C19 genotype-dependent manner decreasing its potential efficacy in human ( 19 ). G. biloba increased the AUC of raltegravir, an HIV integrase inhibitor in humans by 21% and Cmax by 44% which is favorable ( 20 ). Meanwhile, these examples with reduced AUCs in humans are mainly at doses higher than the recommended standardized extracts by European Pharmacopeia ( 21 ).…”

Effect of faldaprevir on raltegravir pharmacokinetics in healthy volunteers

“…In the clinical setting, pharmacokinetics of raltegravir have been shown to vary widely both within and between patients with no reported impact on safety . In this study no serious or severe AEs were reported and there were no discontinuations due to AEs.…”