Abstract
Pediatric tuberculosis is an underappreciated global epidemic estimated to afflict around half a million children worldwide. This problem has historically been overlooked, due in part to their low social status and the difficulty in diagnosis of tuberculosis in children. Children are more susceptible to tuberculosis infection and disease progression, including rapid dissemination into extrapulmonary infection sites. Treatment of pediatric tuberculosis infections has been traditionally built around agents used to treat the adult disease, but the disease pathology, drug pharmacokinetics and the safety window in children differs from the adult disease. This produces additional concerns for drug discovery and development of new agents. This review examines: (i) the safety concerns for current front and second line agents used to treat complex drug resistant infections and how this knowledge can be used to identify, prioritize and dose agents that may be better tolerated in pediatric populations; and (ii) the chemistry and suitability of new drugs in the clinical development pipeline for tuberculosis for the treatment of pediatric infections indicating several new agents may offer significant improvements for the treatment of multi-drug resistant tuberculosis in children.
Keywords: Pediatric tuberculosis, Tuberculosis, tuberculosis drug discovery.
Mini-Reviews in Medicinal Chemistry
Title:Advances in Drug Discovery and Development for Pediatric Tuberculosis
Volume: 16 Issue: 6
Author(s): Daniel Hoagland, Ying Zhao and Richard E. Lee
Affiliation:
Keywords: Pediatric tuberculosis, Tuberculosis, tuberculosis drug discovery.
Abstract: Pediatric tuberculosis is an underappreciated global epidemic estimated to afflict around half a million children worldwide. This problem has historically been overlooked, due in part to their low social status and the difficulty in diagnosis of tuberculosis in children. Children are more susceptible to tuberculosis infection and disease progression, including rapid dissemination into extrapulmonary infection sites. Treatment of pediatric tuberculosis infections has been traditionally built around agents used to treat the adult disease, but the disease pathology, drug pharmacokinetics and the safety window in children differs from the adult disease. This produces additional concerns for drug discovery and development of new agents. This review examines: (i) the safety concerns for current front and second line agents used to treat complex drug resistant infections and how this knowledge can be used to identify, prioritize and dose agents that may be better tolerated in pediatric populations; and (ii) the chemistry and suitability of new drugs in the clinical development pipeline for tuberculosis for the treatment of pediatric infections indicating several new agents may offer significant improvements for the treatment of multi-drug resistant tuberculosis in children.
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Cite this article as:
Hoagland Daniel, Zhao Ying and Lee E. Richard, Advances in Drug Discovery and Development for Pediatric Tuberculosis, Mini-Reviews in Medicinal Chemistry 2016; 16 (6) . https://dx.doi.org/10.2174/1389557515666150722101723
DOI https://dx.doi.org/10.2174/1389557515666150722101723 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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