Safety, tolerability and pharmacokinetics of forsythin in healthy subjects: a double-blinded, placebo-controlled single-dose and multiple-dose escalation and food effect study

Abstract

Background

Forsythin, an active compound from Forsythiae Fructus, has the potential to treat the common cold and influenza through its antipyretic-analgesic, anti-inflammatory and antiviral effects. The safety, tolerability and pharmacokinetic (PK) profile of forsythin were evaluated in healthy Chinese subjects.

Methods

This phase 1a study included three parts: double-blind, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 400, 600 or 800 mg), food effect investigation (100 mg) and multiple-ascending-dose (MAD) (50, 100 or 200 mg TID for 5 days).

Results

Forsythin is safe and tolerable in healthy Chinese subjects. The rates of adverse events (AEs) in the forsythin cohort were similar to those in the placebo cohort. Forsythin is well-absorbed after single or multiple doses and is extensively metabolized. The primary metabolites were aglycone M1, M1 sulphate (M2) and M1 glucuronide (M7). Exposure to forsythin (100 mg) was higher after food intake by approximately 1.4-fold, whereas M2 and M7 did not change. The steady state was reached around three days in the MAD study. Forsythin, M2 and M7 accumulation on day 5 was 1, 3 and 2, respectively.

Conclusions

The safety and PK profiles of forsythin support further evaluation of its efficacy in individuals with the common cold or influenza.

Keywords:

• Forsythin
• pharmacokinetics
• safety
• tolerability
• food effect

Acknowledgments

We would like to thank all healthy volunteers for their participation.

Authors contributions

Ding YH, Zhang H and Fu L conceived the study; Li CY, Wu M, and Zhu XX performed the study; Wang S and Lu MM contributed significantly to the analysis and manuscript preparation; Li CY and Zhang H performed the data analyses and wrote the manuscript; Zhong DF helped perform the analysis with constructive discussions.

Disclosure statement

The authors declare no competing interests.

Data availability statement

The authors confirm that data supporting the findings of this study are available within the article.

Additional information

Funding

This study was funded by Dalian Fusheng Institute of Natural Medicine.