Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Clinical Pharmacology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
Beijing Friendship Hospital, Capital Medical University, Beijing, China.
J Ethnopharmacol. 2021 Jun 28;274:114052. doi: 10.1016/j.jep.2021.114052. Epub 2021 Mar 19.
Scutellaria baicalensis (Huang-Qin in Chinese) is a dry root of the perennial herb Scutellaria baicalensis Georgi, which has been used extensively in current prescriptions. Scutellaria baicalensis is an herb high in flavonoids, and baicalein is the one flavonoid found in the highest amount in Scutellaria baicalensis.
Influenza virus could cause mild respiratory tract illness to severe pneumonia and even death. Baicalein has been proved to be one of the effective components against the influenza virus. However, there have been few reports on human trials of baicalein. The purpose of this study was to evaluate the safety of baicalein in vivo and analyze its pharmacokinetic characteristics.
Three randomized studies were conducted to evaluate the pharmacokinetics (PK), safety, tolerability, and food effects of baicalein tablets. In the 7-month single-dose safety study, 60 subjects were enrolled and randomized to receive 100-800 mg baicalein tablets or placebo. In the single-dose PK study, 40 subjects were enrolled and randomized to receive 200 mg, 400 mg, 600 mg, 800 mg baicalein tablets. In the study of food effect on PK of baicalein, an additional 10 subjects were enrolled in the 400 mg group, this part of the trial lasted for 7 months. Blood and urine samples for PK analysis were collected at a pre-specified time. PK properties in both fasted and fed states were evaluated, as well as safety and tolerability.
Among the 80 subjects who were evaluable for the single-dose safety and tolerability, 56 adverse events (AEs) were observed in 32/80 subjects, of which 49 events were from 28/68 subjects in baicalein group and 7 events were from 4/12 subjects in placebo group. All AEs were mild and resolved without any medical intervention. The most common AEs were elevated high-sensitivity C-reactive protein (hs-CRP) level and high triglycerides. After a single administration of baicalein tablets (200 mg, 400 mg, 600 mg, or 800 mg), C were 280.44, 628.80, 845.20, 489.55 ng/mL; AUC were 2035.57, 2939.31, 4494.88, and 3754.43 h*ng/mL, respectively. And t ranged from 7.80 to 14.91 h. The exposure of baicalein and its metabolites increased in a less than dose-proportional manner.
Baicalein tablets within the studied dose range were safe and well-tolerated in healthy Chinese subjects with no serious or severe adverse effects. Further investigation will be needed to assess the safety and efficacy in the target patients.
黄芩（Huang-Qin 在中国）是多年生草本植物黄芩的干燥根，目前在处方中广泛使用。黄芩是一种富含类黄酮的草药，黄芩素是黄芩中含量最高的一种类黄酮。
流感病毒可引起轻度呼吸道疾病，严重者可导致肺炎甚至死亡。黄芩素已被证明是对抗流感病毒的有效成分之一。然而，关于黄芩素的人体试验报道较少。本研究旨在评估黄芩素体内的安全性，并分析其药代动力学特征。
进行了三项随机研究，以评估黄芩素片的药代动力学（PK）、安全性、耐受性和食物效应。在为期 7 个月的单次剂量安全性研究中，纳入 60 例受试者，并随机分为 100-800mg 黄芩素片或安慰剂组。在单次剂量 PK 研究中，纳入 40 例受试者，并随机分为 200mg、400mg、600mg、800mg 黄芩素片组。在研究黄芩素 PK 对食物的影响时，在 400mg 组中另外纳入 10 例受试者，该部分试验持续 7 个月。在预定时间采集血样和尿样进行 PK 分析。评估禁食和进食状态下的 PK 特性以及安全性和耐受性。
在 80 例可评价单次剂量安全性和耐受性的受试者中，32/80 例受试者出现 56 例不良事件（AE），其中 49 例来自 68/28 例黄芩素组受试者，7 例来自 12/4 例安慰剂组受试者。所有 AE 均为轻度，无需任何医疗干预即可自行缓解。最常见的 AE 是高敏 C 反应蛋白（hs-CRP）水平升高和甘油三酯升高。单次给予黄芩素片（200mg、400mg、600mg 或 800mg）后，Cmax 分别为 280.44、628.80、845.20 和 489.55ng/mL；AUC 分别为 2035.57、2939.31、4494.88 和 3754.43h*ng/mL，t 分别为 7.80-14.91h。黄芩素及其代谢物的暴露量呈非剂量依赖性增加。
在研究剂量范围内，黄芩素片在健康中国受试者中安全且耐受良好，无严重或严重不良事件。需要进一步研究评估其在目标患者中的安全性和疗效。
