Oral meropenem for superbugs: challenges and opportunities

被引:21
|
作者
Raza, Aun [1 ,2 ]
Ngient, Shih Chen [1 ]
Sime, Fekade Bruck [1 ,2 ]
Cabot, Peter J. [1 ]
Roberts, Jason A. [1 ,2 ,3 ,4 ]
Popat, Amirali [1 ,5 ]
Kumeria, Tushar [1 ,6 ]
Falconer, James R. [1 ]
机构
[1] Univ Queensland, Sch Pharm, Woolloongabba, Qld 4102, Australia
[2] Univ Queensland, Sch Pharm, Ctr Translat Antiinfect Pharmacodynam, Brisbane, Qld 4102, Australia
[3] Royal Brisbane & Womens Hosp, Dept Intens Care Med, Brisbane, Qld 4102, Australia
[4] Royal Brisbane & Womens Hosp, Dept Pharm, Brisbane, Qld 4102, Australia
[5] Univ Queensland, Translat Res Inst, Mater Res Inst, Woolloongabba, Qld 4102, Australia
[6] Univ New South Wales, Sch Mat Sci & Engn, Sydney, NSW 2052, Australia
基金
英国医学研究理事会; 澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
P-GLYCOPROTEIN; IN-VITRO; BETA-CYCLODEXTRIN; DRUG-DELIVERY; ANTIBIOTIC-RESISTANCE; SILICA NANOPARTICLES; COMPLEX SYNTHESIS; DNA CLEAVAGE; CACO-2; FORMULATION;
D O I
10.1016/j.drudis.2020.11.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
An increase in the number of multidrug-resistant microbial strains is the biggest threat to global health and is projected to cause >10 million deaths by 2055. The carbapenem family of antibacterial drugs are an important class of last-resort treatment of infections caused by drug-resistant bacteria and are only available as an injectable formulation. Given their instability within the gut and poor permeability across the gut wall, oral carbapenem formulations show poor bioavailability. Meropenem (MER), a carbapenem antibiotic, has broad-spectrum antibacterial activity, but suffers from the above-mentioned issues. In this review, we discuss strategies for improving the oral bioavailability of MER, such as inhibiting tubular secretion, prodrug formulations, and use of nanomedicine. We also highlight challenges and emerging approaches for the development of oral MER.
引用
收藏
页码:551 / 560
页数:10
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