Abstract
We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment.
Highlights
Tuberculosis (TB) is the most common cause of morbidity and mortality from an infectious agent globally [1]
Each of the drugs in the recommended standard anti-TB treatment (ATT) regimen -isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and pyrazinamide (PZA)- has a specific role in sterilizing both semi-dormant and actively multiplying mycobacterial bacilli, required for successful TB treatment outcomes [3](3)
This study provides the first information about concurrently measured plasma and hair INH exposures among children with 100% adherence to ATT, as confirmed via in-person or videoassessed directly observed therapy
Summary
Tuberculosis (TB) is the most common cause of morbidity and mortality from an infectious agent globally [1]. Maintaining adequate adherence to anti-TB drugs for a minimum of 6-months for active TB is essential (but challenging in children, the group at highest risk of TB-related mortality) [2]. Each of the drugs in the recommended standard anti-TB treatment (ATT) regimen -isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and pyrazinamide (PZA)- has a specific role in sterilizing both semi-dormant and actively multiplying mycobacterial bacilli, required for successful TB treatment outcomes [3](3). For global TB control and to reach the target of zero deaths from TB [4], it is critical to optimize existing TB prophylaxis strategies, including INH preventive therapy (IPT), for children < 5years of age, who are at high risk of developing TB after household or other closely-affiliated exposure to active TB [1,2]. Maintaining adequate exposure to IPT is a critical feature to its durable success
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