Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV‐Coinfected Children in India: Recommendations for Dose Modifications
Year: 2017
Type: article
Abstract: This work aimed to evaluate the once‐daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration–time profiles and treatment outcome were obtained from 161 Indian children with drug‐sensitive tuberculosis undergoing thrice‐weekly dosing as per previous Indian pediatric guidelines. The exposure–response relationships were established using a population pharmacokinetic‐pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4–7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (Punfavorable). Model‐based simulation of optimized (Punfavorable ≤ 5%) rifampin once‐daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose‐exposure–response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines.
DOI: 10.1002/cpt.987
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,410
Funders: Svenska Forskningsrådet Formas, Vetenskapsrådet, National Institutes of Health, University of California, San Francisco, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2773907647