Antiviral pharmacodynamics in hollow fibre bioreactors

Pharmacodynamic investigation of antiviral compounds studies the relationship between drug exposure and the virological response. These studies are usually performed in animals and, eventually, in humans and are a very expensive proposition. To find a more efficient and less expensive method for determining pharmacodynamics of antiviral and antimicrobial compounds, the hollow fibre infection model (HFIM) system was developed to perform pharmacodynamic studies in vitro. This review covers the authors' studies on the use of in vitro hollow fibre bioreactor technologies for determining the pharmacodynamics of antiviral compounds for viruses grown in cultured cells, including HIV grown in CD4+ lymphoblastoid cells, vaccinia viruses grown in HeLa-S3 cells and influenza viruses grown in Madin-Darby canine kidney cells. Where possible, correlations between the pharmacodynamic index derived from the in vitro HFIM systems and clinical pharmacodynamic studies are made.