Antimicrobial resistance (AMR) is one of the biggest health threats worldwide. Key to countering AMR is the development of novel anti-infective drugs. The limitations of animal models and clinical trial design have emphasised the importance of nonclinical pharmacokinetics/pharmacodynamics (PK/PD) platforms which provide a detailed understanding of the relationship between the fate of the antimicrobial compound in the body (PK) and the impact of exposure to the compound on the target microbes (PD). This allows us to optimise dosing regimens to maximise the efficacy of antimicrobial compounds (microbial killing) while minimising toxicity and the risk of the emergence of AMR.
What is the HFIM?
The HFIM is a system of pumps, tubing and microfibers that mimics the body, allowing in vitro assessment of anti-infective compounds under more relevant conditions. It consists of a central reservoir and tubing used as a circulating system, and a hollow fibre cartridge with thousands of permeable capillaries. The extra capillary space (ECS) outside the fibres within the cartridge contains the target organism. During operation, the drug-infused growth medium in the central reservoir is continuously pumped to the hollow fibre cartridge, rapidly passing through the capillaries into the ECS. This continuous flow ensures that nutrients, oxygen, and test compounds are continuously refreshed while waste products are removed. To simulate drug clearance, fresh medium is added to the central reservoir effectively diluting the drug from the system. Accordingly, this balance of drug supply/clearance can effectively simulate the drug’s PK profile.
Why choose the HFIM as PK/PD model?
It is the most capable in vitro system for PK/PD determination for anti-infective compounds, against bacteria and fungi. It is a dynamic model capable of simulating almost any given concentration-time profile for one or more compounds, even if they have very different half-lives.. The Hollow Fibre Infection Model is not limited by in vivo model availability, compatibility of PK profiles, dosing or sampling frequency, or study duration, which is extremely important for understanding PK/PD relationships and the risk of AMR over clinically relevant treatment times. Various cartridges with fibres manufactured from different materials are available to optimise the HFIM for microbial growth and compound performance.
In conclusion, the HFIM is a versatile in vitro PK/PD platform which can accelerate the development of antibacterial and antifungal compounds, contributing to the fight against AMR.
If you’d like to learn more about the uses of the Hollow Fibre Infection Model you can download our white paper here