Optimal dosing of 1st line antituberculosis and antiretroviral drugs in children.

Datic - Optimal dosing of 1st line antituberculosis and antiretroviral drugs in children (a pharmacokinetic study)

This trial is registered on clinicaltrials.gov: NCT01637558.

PI: Prof. Helen McIlleron

This pharmacokinetic study enrolled children living with and without HIV up to 12 years and weighing 1.5–30 kg receiving standard first-line antituberculosis treatment between November 2012 to June 2017, in Blantyre, Malawi, and Cape Town, South Africa. Children with acute severe illness were excluded from participation. Intensive pharmacokinetic sampling was performed at least 2 weeks after starting treatment during the initial 2-month intensive phase. Before and after pharmacokinetic evaluation, the standard of care treatment was delivered using interim dosing guidelines for FDCs available in the public health sector at the time, with the goal to come as close as possible to the WHO 2010 guidelines.  At the time of the study, an FDC product providing drug ratios suited to the revised 2010 WHO recommendations was not available. Therefore, on the day of pharmacokinetic evaluation, single drug formulations were used in doses according to WHO 2010 guidelines.

Intensively sampled pharmacokinetic data of rifampicin, isoniazid, and pyrazinamide in pediatric patients in NONMEM format is available. The assay methods were validated over the concentration ranges of 0.117 to 30.0 mg/L for rifampicin, 0.0977 to 26.0 mg/L for isoniazid, and 0.200 to 80.0 mg/L for pyrazinamide.