Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects.
Objectives: Polymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.Methods: An open-label, s...
| Publicado en: | Journal of Infection Vol. 82; no. 2; pp. 207 - 216 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
W B Saunders
Feb2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=148775248&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 148775248 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01634453 8IL jtl: Journal of Infection issn: 01634453 maglogo: N pubinfo: dt: Feb2021 vid: 82 iid: 2 pid: 1351 pub: W B Saunders place: Philadelphia, Pennsylvania artinfo: ui: 148775248 148775248 NLM33453286 148775248 10.1016/j.jinf.2021.01.006 NLM33453286 148775248 ppf: 207 ppct: 9 formats: tig: atl: Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects. aug: au: Liu, Xiaofen Chen, Yuancheng Yang, Haijing Li, Jian Yu, Jicheng Yu, Zhenwei Cao, Guoying Wu, Xiaojie Wang, Yu Wu, Hailan Fan, Yaxin Wang, Jingjing Wu, Jufang Jin, Yi Guo, Beining Hu, Jiali Bian, Xingchen Li, Xin Zhang, Jing affil: Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China sug: subj: Antibiotics Adverse Effects Polymyxin B Adverse Effects China Human Female Male Research Subjects Administration, Intravenous Comparative Studies Multicenter Studies Evaluation Research Validation Studies Randomized Controlled Trials Random Assignment Female Male ab: Objectives: Polymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.Methods: An open-label, single-dose clinical trial was conducted in healthy Chinese subjects. Polymyxin B (sulphate) was administered intravenously at 0.75 or 1.5 mg/kg (n = 10 per dose, 5 males and 5 females) to examine the safety and pharmacokinetics.Results: One female subject in the 1.5-mg/kg group discontinued due to abdominal pain during administration. The most frequently reported adverse events were perioral paraesthesia, dizziness, and numbness of extremities (7/10 subjects in the 0.75-mg/kg group, all subjects in the 1.5-mg/kg group). All neurotoxicity-related events dissipated without treatment within a maximum of 23 h. Notably, abdominal pain (3/5) and vulvar pruritus (2/5), colpitis (2/5) or abnormal uterine bleeding (1/5) were reported in female subjects receiving the 1.5-mg/kg dose. In the 0.75-mg/kg group, the total clearance, volume of distribution and half-life of polymyxin B were 0.028±0.002 L/h/kg, 0.219±0.023 L/kg and 5.44±0.741 h, respectively; similar values were observed in the 1.5-mg/kg group. Urinary recovery was 3.7 ± 1.1% and 8.1 ± 1.3% in the 0.75- and 1.5-mg/kg groups, respectively. Population pharmacokinetics of polymyxin B was consistent with a three-compartment model. The clearance and distribution of the central compartment were 0.027 L/h/kg and 0.071 L/kg, respectively.Conclusions: This study is the first to examine the safety and pharmacokinetics of polymyxin B in healthy subjects. Our results highlight that acute toxicity is a dose-limiting factor for intravenous polymyxin B. pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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