The implications of model-informed drug discovery and development for tuberculosis

被引:14
|
作者
Muliaditan, Morris [1 ]
Davies, Geraint R. [2 ]
Simonsson, Ulrika S. H. [3 ]
Gillespie, Stephen H. [4 ]
Della Pasqua, Oscar [1 ,5 ]
机构
[1] UCL, Sch Life & Med Sci, London, England
[2] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England
[3] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden
[4] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland
[5] GlaxoSmithKline, London, England
关键词
MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; RESISTANT TUBERCULOSIS; PHASE-II; MOXIFLOXACIN; IMPACT; REGIMENS; SAFETY;
D O I
10.1016/j.drudis.2016.09.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Despite promising advances in the field and highly efficacious first-line treatment, an estimated 9.6 million people are still infected with tuberculosis (TB). Innovative methods are required to effectively transition the growing number of compounds into novel combination regimens. However, progression of compounds into patients occurs despite the lack of clear understanding of the pharmacokineticpharmacodynamic (PKPD) relationships. The PreDiCT-TB consortium was established in response to the existing gaps in TB drug development. The aim of the consortium is to develop new preclinical tools in concert with an in silico model-based approach, grounded in PKPD principles. Here, we highlight the potential impact of such an integrated framework on the various stages of TB drug development and on the dose rationale for drug combinations.
引用
收藏
页码:481 / 486
页数:6
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