Background: Anti-tuberculosis drugs display large pharmacokinetic variability, which may be influenced by several factors including body size, genetic differences, and drug-drug interactions. We set out to determine these factors, quantify their effect, and determine the dose adjustments necessary for optimal drug concentrations.
Methods: HIV-infected Ugandan adults with pulmonary tuberculosis treated according to international weight-based dosing guidelines underwent pharmacokinetic sampling (1, 2, and 4 hours after drug intake) at 2, 8, and 24 weeks after treatment initiation.
Results: Between May 2013 and November 2015, we enrolled 268 patients (148 males) with median weight 53.5 (IQR: 47.5 – 59.0) kg and age 35 (IQR: 29 – 40) years. Population pharmacokinetic modelling was used to interpret the data and revealed that patients
Conclusion: Current dosing guidelines lead to lower drug exposure in patients in the lower weight bands. Simply adding one FDC tablet to the current weight band based dosing would address these differences in exposure and possibly improve outcomes. Lower isoniazid exposures due to efavirenz deserve further attention, as does the quality of currently-used drug formulations of anti-TB drugs.