by Zekri Lassout NI, Goyal V, Krantz E, Simon F, Neven A, Eriksson J, Saayman A, Satam V, Ruffell C, Victor S, Chenel M, Celebic A, Caplain H, Gillon J-Y, Deshmukh A, Antarkar A, Sjögren E, Ribeiro I. Clinical and Translational Science 2024, 17(9): e13908. doi: 10.1111/cts.13908
Summary: 5-flucytosine, a treatment for cryptococcal meningoencephalitis, has a limited plasma half-life and must be administered every 6 hours. This poses major practical challenges that may result in treatment failure and death. The authors of this manuscript describe a phase I study in healthy, fed participants that assessed the safety and pharmacokinetic profiles of single-doses of a sustained-release formulation of 5-flucytosine and an immediate-release formulation of 5-flucytosine. The results of this study suggest that the sustained-release formulation of 5-flucytosine is a good candidate for further investigation in future studies in patients. Physiologically-based pharmacokinetic modeling predicts that a 6000 mg dose of this formulation, given twice a day in the fasted state, would be effective and safe.
