by Goyal V, Krantz E, Simon F, Neven A, Eriksson J, Saayman A, Zekri Lassout NI, Louis M, Robinson S, Deshmukh A, Antarkar A, Ruffell C, Victor S, Chenel M, Celebic A, Caplain H, Gillon JY, Ribeiro I. Clinical and Translational Science 2024. doi: 10.1111/cts.13756
Summary: The authors of this manuscript report pharmacokinetic and safety data from a phase I trial of three sustained-release oral pellet formulations of 5-flucytosine for the treatment of cryptococcal meningoencephalitis. These pellets were developed to require less frequent administration than the currently available immediate-release formulation. The safety and pharmacokinetic profiles of a single dose of the three sustained-release formulations (3000 mg at 0h) were compared with those of the immediate-release tablets (Ancotil, 1500 mg at 0h and 1500 mg at 6h) in 42 healthy, fasted participants. All treatments were well-tolerated. The primary pharmacokinetic parameters were significantly lower for the sustained-release formulations than for the immediate-release tablets. Pharmacokinetic modelling indicated twice-daily 6400 mg dosing with the third sustained-release formulation would be optimal for further clinical development.
