title: A Critical Review of the Current Evidence for Measuring Drug Concentrations of First-Line Agents Used to Treat Tuberculosis in Children.
abstract: Tuberculosis is a leading cause of infectious disease-related morbidity and mortality worldwide. Additionally, treatment is complex with most patients requiring combination therapy of first-line agents for multiple months. Children are especially at risk from the medications used to treat tuberculosis and therefore interventions to optimize both efficacy and safety are needed. Protocols exist for therapeutic drug monitoring in tuberculosis patients yet there is a gap in knowledge regarding the extent of any benefits achieved, especially in children. This review aims to summarize and evaluate literature reporting outcomes related to the measurement of drug concentrations of first-line agents used to treat tuberculosis (rifampin, isoniazid, pyrazinamide, ethambutol) in children. Findings showed a lack of strong evidence to support therapeutic drug monitoring in children with tuberculosis. Standard weight-based dosing of first-line agents does not commonly achieve target concentrations yet the effect on clinical outcomes remains unclear. As such, therapeutic drug monitoring should not be recommended currently as a widespread practice for all children with tuberculosis. However, future research should assess any benefit in special populations such as those with relapsing or recurrent disease, or those presenting with adverse drug reactions.
authors.affiliation: College of Pharmacy, Qatar University, PO Box 2713, Doha, Qatar. kjw@qu.edu.qa.
authors.forename: Kyle John
authors.initials: KJ
authors.lastname: Wilby
authors.affiliation: College of Pharmacy, Qatar University, PO Box 2713, Doha, Qatar.
authors.forename: Sara
authors.initials: S
authors.lastname: Shabana
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Fawziah
authors.initials: F
authors.lastname: Marra
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis*; D002648:Child; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents