A Critical Review of the Current Evidence for Measuring Drug Concentrations of First-Line Agents Used to Treat Tuberculosis in Children

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

“…This information can serve as a practical leaflet for clinicians [ 12 , 100 ]. Toxicity and PK related to the clinical outcomes of anti-TB drugs are two crucial aspects of TB research, which have been intensively discussed elsewhere [ 10 , 27 , 31 , 54 , 74 , [100] , [101] , [102] , [103] , [104] , [105] , [106] ]. In the study on AEs surveillance, Ngoc et al [ 104 ] discussed that the administration of long regimens of injectable anti-TB drugs could result in the increased risk of AEs.…”

“…There have been challenges in clinical pharmacokinetic/pharmacodynamic (PK/PD) investigations of anti-TB drugs to unravel these characteristics comprehensively. These are (1) the development and integration of bioanalytical techniques to simultaneously measure concentrations of all active metabolites and concomitant drugs; (2) selecting suitable early outcome indicators presenting the therapeutic responses; (3) the unavailability of effective pharmacovigilance systems in underdeveloped countries; (4) clarification of genetic and non-genetic causes of inter-individual PK variability; (5) difficulties in analyzing PK/PD relationships in clinical data; and (6) determination of PK/PD parameters for special populations (children, pregnant women, HIV-TB coinfection, TB and diabetes comorbidity, renal and hepatic impairment patients) and at the site of actions [ [105] , [106] , [107] ].…”

Revisiting the mutant prevention concentration to guide dosing in childhood tuberculosis

“…First, there are no clear pharmacokinetic targets in children with TB, and efforts to achieve concentrations based on various adult-derived goals have been difficult. 39 Second, more safety data are needed to determine whether an increase in dose will be tolerated. This highlights the need for more pharmacokinetic studies in children with TB in order to correlate outcomes and adverse effects, and the incorporation of the MPC may guide goals for therapeutic doses that also suppress mutant growth.…”