WHO operational handbook on tuberculosis: module 1: prevention: tuberculosis preventive treatment: web annex A: pharmacokinetics modelling and simulation studies for dosages of 6Lfx and 3HP

This web annex to the second edition of the WHO operational handbook on tuberculosis, Module 1: Prevention – tuberculosis preventive treatment, presents pharmacokinetic modelling and simulation studies used to inform dosing recommendations for levofloxacin preventive therapy (6Lfx) and the 3-month once-weekly isoniazid and rifapentine regimen (3HP) in children. The document supports the development of harmonized WHO weight-band dosing approaches for tuberculosis preventive treatment, including for infants and young children previously underrepresented in clinical studies.

The annex describes the methods, datasets and pharmacokinetic models used to simulate drug exposure across paediatric populations from high tuberculosis burden settings. For levofloxacin, simulations were based on population pharmacokinetic models and demographic datasets from countries with high multidrug-resistant tuberculosis burden to propose optimized dosing strategies for dispersible and non-dispersible formulations. For 3HP, the document reviews evidence from TBTC Study 35 and evaluates rifapentine and isoniazid dosing across revised WHO harmonized weight bands, including children aged under 2 years. The publication summarizes assumptions, exposure targets, formulation considerations and simulation results underpinning proposed paediatric dosing recommendations for tuberculosis preventive treatment.