查看文章

BACKGROUND

WHO recommends flucytosine (5FC) as an essential component of cryptococcal meningitis (CM) treatment regimens. The currently available 5FC formulation, an immediate release (IR) tablet, needs to be administered four times a day and is sub-optimal for administration via naso-gastric tube. To address this problem, DNDi is developing a sustained release (SR) formulation. Two PK studies in healthy subjects have already been performed in South Africa, which evaluated the immediate release and SR formulations. A PBPK model was developed using concentration-time profile data from the two studies in healthy volunteers (1).

To assess the risk of the SR formulation leading to over-or underexposure of 5FC in an upcoming Phase 2 trial (due to alterations in the gastrointestinal (GI) tract associated with the disease), PBPK modeling was used to assess the potential impact of the disease on 5FC PK.