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Br J Clin Pharmacol. 2018 Jun 27. doi: 10.1111/bcp.13696. [Epub ahead of print]

Relative bioavailability of bedaquiline tablets suspended in water: Implications for dosing in children.

Author information

1
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
2
Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
3
TASK Applied Science, Cape Town, South Africa.
4
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
5
Department of Pediatrics, State University of New York Stony Brook, New York, USA.
6
Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesada, USA.
7
Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
8
Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Abstract

AIMS:

Bedaquiline is an important novel drug for treatment of multidrug-resistant tuberculosis, but no paediatric formulation is yet available. This work aimed to explore the possibility of using the existing tablet formulation in children by evaluating the relative bioavailability, short-term safety, acceptability and palatability of suspended bedaquiline tablets compared to whole tablets.

METHODS:

A randomized, open-label, two-period cross-over study was conducted in 24 healthy adult volunteers. Rich pharmacokinetic sampling over 48 h was conducted at two occasions 14 days apart in each participant after administration of 400 mg bedaquiline (whole or suspended in water). The pharmacokinetic data were analysed with nonlinear mixed-effects modelling. A questionnaire was used to assess palatability and acceptability.

RESULTS:

There was no statistically significant difference in the bioavailability of the suspended bedaquiline tables compared to whole. The nonparametric 95% confidence interval of the relative bioavailability of suspended bedaquiline tablets was 94-108% of that of whole bedaquiline tablets; hence, the predefined bioequivalence criteria were fulfilled. There were no Grade 3 or 4 or serious treatment emergent adverse events recorded in the study and no apparent differences between whole tablets and suspension regarding taste, texture or smell.

CONCLUSIONS:

The bioavailability of bedaquiline tablets suspended in water was the same as for tablets swallowed whole and the suspension was well tolerated. This suggests that the currently available bedaquiline formulation could be used to treat multidrug-resistant tuberculosis in children, to bridge the gap between when paediatric dosing regimens have been established and when a paediatric dispersible formulation is routinely available.

KEYWORDS:

bedaquiline; bioavailability; paediatric dosing; population PK; suspended tablets

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