The use of pre-sterilized, double-bagged FiberCell polysulfone C2011, or cellulosic C3008 hollow fibre cartridge modules, is widely reported for this application. See : [references]
Precisely mimic any human concentration-time profile for your antimicrobial drug candidate or lead compound
Ideal for testing short half-life drug and combinations
Take multiple samples over time
Study the emergence of resistance over extended periods, months if necessary
Evaluate total kill
Co-cultivate different cell types, e.g. mammalian cells, bacteria, viruses
Rank new antimicrobial compounds by first testing a range of half-lives/exposure times in vitro
Hollow Fibre 2-compartment PK/PD system
How does it work?
Nutrient broth with test drugs is rapidly circulated at 60 ml per minute using the Duet Pump through the porous-walled hollow fibres (3 fibres only are shown here for simplicity). At this high flow rate drug concentrations will equilibrate throughout the complete loop including reservoir, extracapillary “PD compartment”, and the luminal “PK compartment”.
Drug exposure of the cells in the extracapillary compartment is precisely controlled by diluent addition and waste removal as with the classic chemostat single compartment model.
Endorsed by the EMA for PK/PD studies with Mtb.
“The Agency has published on 7 February 2015 a qualification opinion on the in-vitro hollow fiber system model of tuberculosis (TB) (EMA/CHMP/SAWP/47290/2015 Corr.).
Investigate the Emergence of Drug Resistance
The system is ideal for longer-term PK/PD studies to investigate the emergence of antimicrobial resistance, for example. It offers a level of precision and economy unattainable with animal models and bridges the gap between static assays, animal models and clinical trials
Essential reading : The Hollow Fiber Infection Model, Principles and Practice by J.J. Cadwell [FREE DOWNLOAD]