An assay toolkit for anti-tuberculosis drugs in the hollow fiber system

The hollow-fiber system for tuberculosis (HFS-TB) is an in vitro pharmacokinetic/pharmacodynamic (PKPD) tool qualified by the European Medicines Agency to support anti-TB drug development. It can simulate PK parameters of antimicrobials and feed in silico models to inform phase II/III clinical trials. Yet, its implementation is challenging due to lack of consolidated technical guidelines, such as the compatibility of drugs with the most commonly used types of HFS-TB cartridges. Herein, we uncovered the compatibility of 10 anti-TB drugs alone: bedaquiline, clarithromycin, delamanid, ethambutol, isoniazid, linezolid, moxifloxacin, pretomanid, rifampicin, and rifapentine; and of a combination, bedaquiline-pretomanid-linezolid. The most hydrophilic compounds were within the compatibility range with all fibers; whereas the lipophilic ones required adjustments to be used in the system. Also, polysulfone and cellulose fibers were the most suitable for the tested drugs. Our data strengthen the importance of these preliminary studies and provide a useful toolkit toward wider HFS-TB implementation.