Human Safety and Pharmacokinetics Study of Orally Administered Icariin: Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Preclinical literature suggests that icariin, a flavonoid found in Epimedium, may have potential for medical and psychiatric conditions. The objective of this study was to examine the safety, tolerability, and pharmacokinetics of orally administered icariin at doses of 100 to 1,680 mg/day in 24 healthy adult participants. Cognition, mood, and side effects were assessed over 5 days. Multiple blood samples were obtained over 24 hours to assess bioavailability and pharmacokinetics. Data were analyzed using a Wilcoxon signed rank test and Mann-Whitney U test. At all doses, either very low or undetectable blood levels of icariin were observed, demonstrating the low bioavailability of the oral formulation and preventing a determination of pharmacokinetic properties. No significant between-group differences were observed on side effect scales, either by self-report, or on cognitive assessments. A statistically significant, but not clinically significant, increase in self-reported depressive symptom severity was observed with icariin relative to placebo. Tolerability of icariin was good except at the highest dose. Two participants receiving 1,680 mg of icariin discontinued the study drug due to gastrointestinal symptoms. Bioavailability of oral icariin appears to be low at all doses tested. Although icariin appears generally to have a favorable tolerability profile, the highest doses may be associated with gastrointestinal distress. Different drug formulation and delivery method may be needed to assess the pharmacokinetic profile of icariin adequately.