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Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers

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A Letter to the Editor to this article was published on 12 October 2016

Abstract

Background and Objectives

Baicalein, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, is a neuroprotective agent under development to treat Parkinson’s disease. This study investigated the pharmacokinetics, safety and tolerability of baicalein after a multiple-ascending-dose protocol in healthy Chinese volunteers.

Methods

In this single-center, double-blind, placebo-controlled, parallel-group study, participants were randomized to receive baicalein (n = 8 per dose regimen) or placebo (n = 2 per dose regimen). Dosing regimens were 200, 400, and 800 mg once daily on days 1 and 10, twice daily on days 3–9. Plasma, urine, and feces samples were assayed for baicalein and its predominant metabolite baicalin using validated HPLC–MS/MS methods. Pharmacokinetic parameters were computed using standard non-compartmental analysis. Dose proportionality was assessed with a method combining equivalence criterion and power model. Drug safety and tolerability were assessed by monitoring adverse events and laboratory parameters.

Results

Thirty-three of 36 enrolled participants completed the study. A total of 44 adverse events occurred in 23 participants. A steady-state concentration of analytes in plasma was achieved on day 8 after repeated dosing. Analytes concentrations and exposure increased with increasing dose. The dose proportionality constant (β) for AUCss of baicalein and baicalin was 0.922 (90 % confidence interval, 0.650–1.195) and 0.942 (90 % confidence interval, 0.539–1.345), respectively. The accumulation index varied from 1.66 to 2.07 for baicalein and from 1.68 to 2.45 for baicalin.

Conclusion

In dose range of 200–800 mg, multiple-dose oral baicalein administration was safe and well tolerated, dose proportionality was inconclusive, and no serious accumulation of baicalein was observed.

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Acknowledgments

We are grateful for the following persons for their assistance in the study: Jiamin Chi, Huili Liu, Jianhua Yang, Huihong Qi, Panpan Xie, Taifeng Li, Yi Jin, Chunxiao Li, Wenjing Hou, and Kongcai Zhu. We thank all volunteers who participated in this study.

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Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Hongxian Pang & Gang Cheng

  2. Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, No.1 Dahua Road, Beijing, 100730, People’s Republic of China

    Hongxian Pang, Wei Xue, Aixin Shi, Min Li, Yang Li, Guoying Cao, Bei Yan, Fan Dong & Xin Hu

  3. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical CO.LTD, Jiangsu, People’s Republic of China

    Wei Xiao

  4. Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China

    Guorong He & Guanhua Du

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  1. Hongxian Pang
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  2. Wei Xue
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  4. Min Li
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  11. Guanhua Du
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  13. Gang Cheng
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Corresponding authors

Correspondence to Aixin Shi or Gang Cheng.

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Funding

This study was funded by Kanion pharmaceutical Limited Corporation (Jiangsu, PR China).

Conflict of interest

Wei Xiao was an employee of Kanion pharmaceutical Limited Corporation (Jiangsu, PR China) at the time of conduct of the studies, and hold stock in the company. All other authors report no conflicts of interest. All authors had access to the study data and made the final decision about where to publish these data.

Ethical approval

The study protocol received approval by the Beijing Hospital Ethics Committee, Beijing, and was conducted in accordance with Good Clinical Practice (GCP), including the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants prior to their inclusion in the study.

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Pang, H., Xue, W., Shi, A. et al. Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers. Clin Drug Investig 36, 713–724 (2016). https://doi.org/10.1007/s40261-016-0418-7

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