Pharmacokinetics and pharmacodynamics of the nitroimidazole DNDI-0690 in mouse models of cutaneous leishmaniasis

by Wijnant G-J, Croft SL, de la Flor R, Alavijeh M, Yardley V, Braillard S, Mowbray C, Van Bocxlaer K. Antimicrobial Agents and Chemotherapy 2019, 63:e00829-19.

Summary: Nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, the authors investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative Leishmania pathogen in murine models of CL. Two doses of 50 mg/kg DNDI-0690 were sufficient to reduce the Leishmania mexicana parasite load by 100-fold, while 6 such doses were needed to achieve similar killing of Leishmania major. A combination of rapid accumulation and potent activity in the Leishmania-infected dermis indicates the potential of DNDI-0690 as a novel oral treatment for CL.

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