Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis

Crass Ryan L.; Al Naimi Tamara; Wen BoSouza ErnaneMurray SusanPai Manjunath P.Jia Shijing

首页> 外文期刊>Antimicrobial agents and chemotherapy. >Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis

【24h】

Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis

机译：Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

The optimal polymyxin B dosage needed to achieve an efficacy target of 50 to 100 mg . h/liter when treating multidrug-resistant bacterial infections in adult cystic fibrosis (CF) patients is unclear. The pharmacokinetics of intravenous polymyxin B were evaluated to better inform dosing. This was a prospective, observational pharmacokinetic (PK) study of nine CF adults receiving intravenous polymyxin B as part of usual clinical care. Doses preceding PK sampling ranged from 50 to 100 mg every 12 h. Five PK samples were collected following the fourth or fifth dose and concentrations of polymyxin subcomponents B1 and B2 were quantified using liquid chromatography mass spectrometry (LC-MS). Population PK (NONMEM software) analysis was performed using pooled polymyxin B1+B2 concentrations. Participants were Caucasian, predominantly male, with mean age and weight of 31 years (range 21 to 57 years) and 58.0 kg (range 38.3 to 70.4 kg), respectively. A 1-compartment zero-order infusion and linear elimination model adequately described the data with estimated clearance and volume of distribution being 2.09 liters/h and 12.7 liters, respectively, corresponding to a 4.1 h mean half-life (t(1/2)). Although body weight was observed to influence the volume of distribution, a fixed dose of 75 mg every 12 h was predicted to achieve the target steady-state exposure. Neurotoxicities were reported in all patients, with acute kidney injury events in two patients. These events resolved within 2 to 4 days after discontinuing polymyxin B. Fixed maintenance dosing of polymyxin B without loading is predicted to achieve the targeted therapeutic exposure in CF adults. Treatment-limiting neurotoxicities are very common in this population.

著录项

来源
《Antimicrobial agents and chemotherapy.》 |2021年第10期|共12页
作者
Crass Ryan L.; Al Naimi Tamara; Wen BoSouza ErnaneMurray SusanPai Manjunath P.Jia Shijing;
展开▼
作者单位

Ann Arbor Pharmacometr Grp, Ann Arbor, MI USA;

Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA;

Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类治疗学;
关键词
body weight; neurotoxocity; population pharmacokinetics;

Pharmacokinetics of Polymyxin B in Hospitalized Adults with Cystic Fibrosis

摘要

著录项

相关主题

期刊订阅