Bioavailability of three novel oral, sustained-release pellets, relative to an immediate-release tablet containing 500 mg flucytosine: A randomized, open-label, crossover study in healthy volunteers

PBPK & PBBM

Infectious Diseases

Clin Transl Sci. 2024 Mar;17(3):e13756

Goyal V, Krantz E, Simon F, Neven A, Eriksson J, Saayman A, Lassout NIZ, Louis M, Robinson S, Deshmukh A, Antarkar A, Ruffell C, Victor S, Chenel M, Celebic A, Caplain H, Gillon JY, Ribeiro I

About formulation and dose selection for further clinical development of a sustained release formulation in the treatment of cryptococcal meningoencephalitis.

The article includes the findings of a phase I trial conducted in South Africa, examining three sustained-release (SR) oral pellet formulations (B, C and D) of 5-flucytosine. These formulations aim to reduce the frequency of administration, potentially providing a more convenient alternative to the current immediate release (IR) formulation, which is dosed 4 times daily. While the SR pellets showed lower maximum observed plasma concentration and area under the concentration-time profiles compared to the IR tablets, PBPK modeling suggest that a dosing regimen of twice-daily 6400 mg dose of SR formulation D under fasted conditions could maintain steady-state drug exposure levels within the therapeutic boundaries.

This research contributes to combating infectious diseases, and by innovative formulations and optimization of dosing, aim to enhance treatment accessibility and efficacy, ultimately improving lives of those affected by cryptococcal meningoencephalitis.