Aim: Delamanid is a novel drug for the treatment 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 vs swallowed whole, was investigated in a phase I, four-period, crossover study. Two of three dose strengths of delamanid (25, 50 or 100 mg) were given to healthy adult participants, in both whole and dispersed forms, with a 7-day washout period. Blood samples were collected over 168 h 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 a 90% confidence interval of 99.7-114%, fulfilling bioequivalence criteria. 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.
Keywords: bioequivalence; delamanid; population pharmacokinetics; relative bioavailability; tuberculosis.
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.