LAUSR

AIM Delamanid is a novel drug to treat of drug-resistant tuberculosis, manufactured as 50 mg solid and 25 mg dispersible tablets. We evaluated the effects of dispersing the 50 mg tablet, focusing on the relative bioavailability. METHODS Delamanid 50 mg tablets administered dispersed versus swallowed whole, was investigated in a phase I, four-period, cross-over study. Two of three dose strengths of delamanid (25, 50 or 100 mg) were given to healthy adult participants, both in whole and dispersed forms, with seven-day washout period. Blood samples were collected over 168 hours after each dose. Delamanid and its metabolite DM-6705 were analysed with a validated liquid chromatography tandem mass spectrometry assay. The pharmacokinetics of both analytes were analysed using nonlinear mixed-effect modelling. Palatability and acceptability were determined using a standardized questionnaire. RESULTS Twenty-four participants completed the study. The bioavailability of dispersed tablets was estimated to be 107% of whole tablets, with 90% confidence interval of 99.7-114%, fulfilling bioequivalence criterion. The two formulations were not significantly different regarding either bioavailability or its variability. Bioavailability increased at lower doses, by 34% (26-42%) at 50 mg and by 74% (64-86%) at 25 mg, relative to 100 mg. The majority of participants (93%) found the dispersed formulation acceptable in palatability across all delamanid doses. CONCLUSIONS Dispersed 50 mg delamanid tablets have similar bioavailability to tablets swallowed whole in adult volunteers. This can be an option for children and other patients who cannot swallow whole tablets, improving access to treatment.