Chang, Yong S, Li, Si-Yang, Pertinez, Henry, Betoudji, Fabrice, Lee, Jin, Rannard, Steven P 
ORCID: 0000-0002-6946-1097, Owen, Andrew ORCID: 0000-0002-9819-7651, Nuermberger, Eric L and Ammerman, Nicole C
(2023)
Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 67 (7).
e0048123-.
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Chang et al. aac.00481-23.pdf - Open Access published version Download (1MB) | Preview |
Abstract
Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication. Rifapentine and rifabutin have antituberculosis activity and physiochemical properties suitable for LAI formulation, but there are limited data available for determining the target exposure profiles required for efficacy in TPT regimens. The objective of this study was to determine exposure-activity profiles of rifapentine and rifabutin to inform development of LAI formulations for TPT. We used a validated paucibacillary mouse model of TPT in combination with dynamic oral dosing of both drugs to simulate and understand exposure-activity relationships to inform posology for future LAI formulations. This work identified several LAI-like exposure profiles of rifapentine and rifabutin that, if achieved by LAI formulations, could be efficacious as TPT regimens and thus can serve as experimentally determined targets for novel LAI formulations of these drugs. We present novel methodology to understand the exposure-response relationship and inform the value proposition for investment in development of LAI formulations that have utility beyond latent tuberculosis infection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Mycobacterium tuberculosis, latent tuberculosis, rifapentine, rifabutin, long-acting injectable |
| Divisions: | Faculty of Health and Life Sciences Faculty of Science and Engineering > School of Physical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 27 Jul 2023 14:25 |
| Last Modified: | 10 Aug 2023 07:39 |
| DOI: | 10.1128/aac.00481-23 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3171945 |
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