A First-in-Human Safety, Tolerability, and Pharmacokinetics Study of Benapenem in Healthy Chinese Volunteers
| Autor: | Min-Ji Wei, Xi-Wei Ji, Meng-Ying Liu, Yan Liu, Yan Ma, Yan Zhu, Yuan Lv, Ya-Hong Xia, Zi-Sheng Kang, Cai-Yun Zhao, Ji-Hong Tian |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male China medicine.medical_specialty Adolescent Clinical Therapeutics Placebo Young Adult 03 medical and health sciences Double-Blind Method Pharmacokinetics Internal medicine Humans Medicine Pharmacology (medical) Dosing Infusions Intravenous Adverse effect 030304 developmental biology Pharmacology 0303 health sciences Dose-Response Relationship Drug 030306 microbiology business.industry Infusion time Safety tolerability First in human Middle Aged Healthy Volunteers Infectious Diseases Carbapenems Tolerability Area Under Curve Female business |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 63 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Objective: The objective of this trial is to investigate the safety, tolerability and pharmacokinetics (PK) of benapenem administrated by single or multiple intravenous infusions in healthy Chinese volunteers. Methods: The trial was divided into 3 parts. 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, 1000, 2000 or 3000 mg, respectively. The effects of intravenous infusion time on the subjects of 250, 500 and 1000 mg group were explored. Part B: 12 subjects were enrolled in a single-dose PK study under fasting conditions receiving 250, 500 or 1000 mg of benapenem for injection. Part C: 36 subjects were given 250, 500 and 1000 mg of benapenem for injection once daily for 7 consecutive days. Findings: 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. Implications: The PK and safety profiles of benapenem in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (Part A, Part B & Part C has been registered at ClinicalTrials.gov under identifier NCT03588156, NCT03578588 & NCT03570970, respectively.) |
| Databáze: | OpenAIRE |
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