Pharmacokinetics and efficacy of liposomal polymyxin B in a murine pneumonia model.
Pharmacokinetics and efficacy of liposomal polymyxin B in a murine pneumonia model.
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DOI：
10.1016/j.ijantimicag.2013.07.009
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发表时间：
2013-12
影响因子：
10.8
通讯作者：
Tam VH
中科院分区：
文献类型：
--
作者：
He J;Abdelraouf K;Ledesma KR;Chow DS;Tam VH
多粘菌素B（PB）越来越多地用作多重耐药（MDR）革兰氏阴性菌感染的最后治疗。在本研究中，研究了PB脂质体制剂的血清和上皮衬里液（ELF）药代动力学和疗效。将两组24只Swiss韦伯斯特小鼠静脉内给予PB脂质体或PB水溶液，3 mg/kg。收集血清和ELF样品长达6小时，以定量主要PB组分。用临床MDR铜绿假单胞菌菌株感染三组血小板减少小鼠（n = 6/组），随后每6小时静脉内施用PB脂质体或PB水溶液（3 mg/kg）或每6小时假（无药物）脂质体。在治疗24小时后定量动物肺组织中的细菌负荷，并使用单因素ANOVA进行比较。通过Kaplan-Meier分析和对数秩检验评价感染动物随时间的存活率（n = 10/组）。在药代动力学研究中，对于各种主要PB组分，脂质体和水溶液组之间ELF中的AUC比值范围为4.6 - 11.1。在有效性研究中，对于菌株PA 9019，在脂质体组中观察到显著较低的细菌负荷（3.8 ± 0.7与水溶液组中的7.9 ± 0.8 log 10 CFU/g），随后延长了感染动物的存活期。在这项研究中，PB脂质体制剂治疗产生了更高的药物渗透到肺ELF中，这导致了上级疗效。然而，需要对PB脂质体制剂的临床效用进行进一步研究。
Polymyxin B (PB) is increasingly used as the last treatment for multidrug-resistant (MDR) Gram-negative bacterial infections. In this study, serum and epithelial lining fluid (ELF) pharmacokinetics and the efficacy of a PB liposomal formulation were investigated. Two groups of 24 Swiss Webster mice were intravenously administered PB liposomes or PB aqueous solution at ca. 3 mg/kg. Serum and ELF samples were collected for up to 6 h to quantify major PB components. Three groups of neutropenic mice (n = 6/group) were infected with a clinical MDR Pseudomonas aeruginosa strain followed by intravenous administration of PB liposomes or PB aqueous solution at 3 mg/kg every 6 h or sham (drug-free) liposomes every 6 h. Bacterial burden in animal lung tissues was quantified after 24 h of therapy and was compared using one-way ANOVA. Survival of infected animals over time (n = 10/group) was evaluated by Kaplan–Meier analysis and log-rank test. In the pharmacokinetic study, the AUC ratio in ELF between liposome and aqueous solution groups ranged from 4.6 to 11.1 for various major PB components. In the efficacy study, for strain PA 9019 a significantly lower bacterial burden was seen in the liposomal group (3.8 ± 0.7 vs. 7.9 ± 0.8 log10 CFU/g in the aqueous solution group), which subsequently prolonged survival of infected animals. In this study, treatment with a PB liposomal formulation yielded higher drug penetration into pulmonary ELF, which resulted in superior efficacy. However, further investigations on the clinical utility of the PB liposomal formulation are warranted.
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影响因子：
5.8
作者：
Alipour, Misagh;Halwani, Majed;Suntres, Zacharias E.
通讯作者：
Suntres, Zacharias E.
影响因子：
120.7
作者：
Fagon, JY;Chastre, J;Gibert, C
通讯作者：
Gibert, C
影响因子：
7.5
作者：
COUNE, A
通讯作者：
COUNE, A
影响因子：
4.4
作者：
Chen, Luke F.;Kaye, Donald
通讯作者：
Kaye, Donald
DOI：
10.1164/ajrccm.159.4.9807050
发表时间：
1999-04-01
影响因子：
24.7
作者：
Heyland, DK;Cook, DJ;Brun-Buisson, C
通讯作者：
Brun-Buisson, C