Cheng Junlin, Long Jun, Zhang Jingjing, Han Le, Hu Yunfang, Liu Jianghui, Qiu Runze, Zhu Zhibin, Fan Hongwei
Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Nanjing Hongqiao Pharmaceutical Technology Research Institute Co Ltd, Nanjing, China.
Front Pharmacol. 2023 Apr 13;14:1146309. doi: 10.3389/fphar.2023.1146309. eCollection 2023.
Salvianolic acid B (Sal B) is one of the main active ingredients of Sa Bunge. In China, many traditional Chinese medicines have been modified into injections for higher bioavailability and better efficacy. Salvianolic acid injection has been widely used in the clinic. This phase 1, randomized, double-blind, placebo-controlled, single-center study aimed to evaluate the safety, tolerance, and pharmacokinetics of Sal B injection in healthy Chinese volunteers. For the single-ascending-dose study, forty-seven healthy volunteers were randomly divided into 25, 75, 150, 200, 250, and 300 mg groups. For the multiple-ascending-dose study, sixteen healthy volunteers were randomly divided into 150 and 300 mg groups. In each group, volunteers were treated with Sal B or placebo randomly. Their safety was evaluated by a skin test, physical examination, vital sign, laboratory examination, 12-lead electrocardiogram, Holter, and clinical symptoms and signs. Blood samples were collected in 75, 150, and 300 mg single-ascending-dose study groups and 150 mg multiple-ascending-dose study groups to determine the concentration of salvianolic acid B. In single-ascending-dose study groups, there were 41 adverse events in 24 cases (51.1%, 24/47). In multiple-ascending-dose study groups, there were 13 adverse events in eight cases (50.0%, 8/16). Sixty-six volunteers received the skin test, and three of them were excluded because of the positive result. Adverse events related to the treatment included increased alanine aminotransferase (4.0%), increased bilirubin (2.0%), increased creatinine kinase-MB (2.0%), increased brain natriuretic peptide (8.0%), increased urine N-acetyl-β-D-glucosidase (4.0%), dizziness (2.0%), and chest discomfort (2.0%). No serious adverse events occurred. No volunteers withdrew from the trial. Peak plasma concentration and the area under the plasma concentration-time curve of salvianolic acid B progressively increased in a dose-dependent manner in 75, 150, and 300 mg single-ascending-dose study groups. There was no accumulation after 5 consecutive days of administration of 150 mg salvianolic acid B. Salvianolic acid B injections administered up to 300 mg in a single dose and 250 mg for 5 consecutive days showed excellent safety and tolerability in healthy Chinese volunteers. www.chinadrugtrials.org.cn, identifier CTR20192236.
丹酚酸B（Sal B）是丹参的主要活性成分之一。在中国，许多传统中药已被制成注射剂，以提高生物利用度和疗效。丹酚酸注射液已在临床上广泛应用。这项1期随机、双盲、安慰剂对照、单中心研究旨在评估丹酚酸B注射液在健康中国志愿者中的安全性、耐受性和药代动力学。在单剂量递增研究中，47名健康志愿者被随机分为25、75、150、200、250和300mg组。在多剂量递增研究中，16名健康志愿者被随机分为150和300mg组。每组志愿者随机接受丹酚酸B或安慰剂治疗。通过皮肤试验、体格检查、生命体征、实验室检查、12导联心电图、动态心电图监测以及临床症状和体征来评估其安全性。在75、150和300mg单剂量递增研究组以及150mg多剂量递增研究组中采集血样，以测定丹酚酸B的浓度。在单剂量递增研究组中，24例（51.1%，24/47）出现41例不良事件。在多剂量递增研究组中，8例（50.0%，8/16）出现13例不良事件。66名志愿者接受了皮肤试验，其中3人因结果阳性被排除。与治疗相关的不良事件包括谷丙转氨酶升高（4.0%）、胆红素升高（2.0%）、肌酸激酶同工酶MB升高（2.0%）、脑钠肽升高（8.0%）、尿N-乙酰-β-D-葡萄糖苷酶升高（4.0%）、头晕（2.0%）和胸部不适（2.0%）。未发生严重不良事件。没有志愿者退出试验。在75、150和300mg单剂量递增研究组中，丹酚酸B的血浆峰浓度和血浆浓度-时间曲线下面积呈剂量依赖性逐渐增加。连续5天给予150mg丹酚酸B后无蓄积现象。单剂量给予高达300mg、连续5天给予250mg的丹酚酸B注射液在健康中国志愿者中显示出良好的安全性和耐受性。www.chinadrugtrials.org.cn，标识符CTR20192236 。
