• 作者：Shashikant Srivastava^a ; Jotam G. Pasipanodya^a ; Geetha Ramachandran^b ; Devyani Deshpande^a ; Stephen Shuford^c ; Howland E. Crosswell^c ; Kayle N. Cirrincione^a ; Carleton M. Sherman^a ; Soumya Swaminathan^b ; Tawanda Gumbo^a ; ^b ; ^{tawanda.gumbo@BSWhealth.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Disseminated tuberculosis ; Pediatric ; Hepatotoxicity ; 3D liver hollow fiber model
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：6
• 期：Complete
• 页码：126-138
• 全文大小：1904 K

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We designed a pre-clinical of disseminated for simultaneous identification of toxicity and efficacy in children.

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The system is a co-culture of infected monocytes and 3 dimensional organotypic liver recapitulating children pharmacokinetics.

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Pyrazinamide, central drug in treatment regimen, had no effect as monotherapy or contribute to the combination therapy.

Due to fear of toxicity children are often not involved in clinical trials, and as a result the optimal treatment regimens are often lacking. As an example, toddlers and babies develop disseminated tuberculosis but are treated with regimens designed for adults with lung cavity disease. We designed a “glass-mouse” model of disseminated tuberculosis that simultaneously tests for the efficacy and toxicity of the anti-tuberculosis drugs for children with disseminated disease. We found that while not causing dose-dependent liver toxicity, one of the central drugs used to treat this children is likely not efficacious.