In uninfected rats, an oral dose of 25 mg/kg, the dose corresponding to a 100% cure rate in mice, led to approximately a twofold increase in Cmax (18.2 μg/mL) and a fourfold increase in AUC0-24 h (291 h•μg/mL) compared to mice, with oral clearance (CL/F) registering at 0.092 L/kg/h. The time to reach the maximum concentration (tmax) remained consistent with that in mice at approximately 8 hours. In cynomolgus monkeys, Acoziborole was administered at 2 mg/kg intravenously on the first day and 10 mg/kg nasogastrically on the eighth day. The pharmacokinetic profile in monkeys highlighted exceptional characteristics, with a systemic clearance (CL) of 0.022 L/h/kg, a volume of distribution (Vdss) of 0.656 L/kg, and areas under the concentration-time curve (AUC) of 78.8 h•μg/mL for AUC0-24 h and 94.4 h•μg/mL for AUC0-inf following intravenous administration, underscoring Acoziborole's potential as a therapeutically relevant antiprotozoal agent across different species^[1].

Acoziborole demonstrates strong in vitro efficacy against key strains of Trypanosoma brucei, including T. b. rhodesiense and T. b. gambiense. When tested in whole cell assays, acoziborole shows significant potency against strains of T. b. brucei, T. b. rhodesiense, and T. b. gambiense, with IC50 values ranging from approximately 0.07 µg/mL to 0.37 µg/mL after a 72-hour exposure period. Specifically, for the T. b. brucei S427 strain, acoziborole's minimal inhibitory concentration (MIC) is determined to be 0.6 µg/mL, which is about twice the IC50 value measured for this particular strain. Remarkably, while acoziborole is potent against trypanosomal strains, it does not significantly inhibit the proliferation of mammalian cells, as evidenced by its lack of effect on the L929 mouse cell line at concentrations up to 50 µg/mL. Furthermore, acoziborole's potential to interfere with cytochrome P450 (CYP) enzymes has been assessed through P450-Glo assays targeting human isoforms such as CYP3A4, CYP1A2, CYP2C19, CYP2C9, and CYP2D6, where all IC50 values for acoziborole are recorded to be greater than 10 µM, indicating a low likelihood of cytochrome P450 mediated drug interactions^[1].