Denti P, Wasmann RE, van Rie A, et al. - In 2010, dosing guidelines for treatment of childhood tuberculosis were revised by the WHO. In this study, first-line antituberculosis drug exposures were investigated under these guidelines, dose optimization was explored using the current dispersible fixed-dose combination (FDC) table of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg , and a new FDC with revised weight-bands was suggested.

• Pharmacokinetic sampling was performed in children with drug-susceptible tuberculosis while receiving first-line tuberculosis drugs as single formulations according to the 2010 WHO recommended doses.

• One, 2, 3, or 4 FDC tablets (rifampicin/isoniazid/pyrazinamide 75/50/150 mg) were administered daily for 4-8, 8-12, 12-16, and 16-25 kg weight-bands, respectively, to 180 children.

• Low rifampicin exposures were recorded with the current pediatric FDC doses.

• The current FDCs did not result in achievement of optimal dosing of all drugs.

• Exposures to all three drugs improved with providing 1, 2, 3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6, 6-13, 13-20 and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism.