Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.
Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
Antimicrob Agents Chemother. 2019 Feb 26;63(3). doi: 10.1128/AAC.02188-18. Print 2019 Mar.
The objective of this trial was to investigate the safety, tolerability, and pharmacokinetics (PK) of benapenem administered by single or multiple intravenous infusions in healthy Chinese volunteers. The trial was divided into 3 parts. In part A, 94 subjects were enrolled in a double-blind, placebo-controlled, sequential-ascending-single-dose study. The subjects were randomly assigned to groups receiving placebo or benapenem for injection at doses of 62.5, 125, 250, 500, 1,000, 2,000, or 3,000 mg. The effects of intravenous infusion time on the subjects of 250-, 500-, and 1,000-mg groups were explored. In part B, 12 subjects were enrolled in a single-dose PK study under fasting conditions and received 250, 500, or 1,000 mg of benapenem for injection. In part C, 36 subjects were given 250, 500, and 1,000 mg of benapenem for injection once daily for 7 consecutive days. The results showed that benapenem for injection was well tolerated during the studies. The major observed adverse events were mild, and all were resolved spontaneously without any medical intervention. Benapenem was mainly excreted through the kidneys in the form of parent molecule and metabolites. The PK and safety profiles of benapenem in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (Part A, part B, and part C have been registered at ClinicalTrials.gov under identifiers NCT03588156, NCT03578588, and NCT03570970, respectively.).
本试验旨在研究健康中国志愿者单次或多次静脉输注苯唑西林的安全性、耐受性和药代动力学（PK）。试验分为 3 部分。在 A 部分，94 名受试者参加了一项双盲、安慰剂对照、序贯递增单剂量研究。受试者随机分为接受安慰剂或注射用苯唑西林的组，剂量分别为 62.5、125、250、500、1000、2000 或 3000mg。探索了静脉输注时间对 250、500 和 1000mg 组受试者的影响。在 B 部分，12 名受试者参加了一项禁食条件下的单剂量 PK 研究，接受 250、500 或 1000mg 注射用苯唑西林。在 C 部分，36 名受试者每天一次接受 250、500 和 1000mg 注射用苯唑西林，连续 7 天。结果表明，试验期间注射用苯唑西林耐受良好。主要观察到的不良事件为轻度，且无需任何医疗干预均自行缓解。苯唑西林主要以原形分子和代谢物的形式经肾脏排泄。健康中国志愿者中苯唑西林的 PK 和安全性特征支持其在未来临床研究中的每日一次给药。（A 部分、B 部分和 C 部分已在 ClinicalTrials.gov 上分别以 NCT03588156、NCT03578588 和 NCT03570970 进行注册。）。
