Pharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous Leishmaniasis.

Wijnant, Gert-Jan
Croft, Simon L
de la Flor, Raul
Alavijeh, Mo
Yardley, Vanessa
Braillard, Stéphanie
Mowbray, Charles
Van Bocxlaer, Katrien

Open PDF

Open link

Publication date

July 2019

DOI

10.1128/AAC.00829-19

Publisher

American Society for Microbiology

Abstract

The 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, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative Leishmania pathogen. This study evaluates the pharmacokinetics (PK) and pharmacodynamics (PD) of DNDI-0690 in mouse models of CL. Skin microdialysis and Franz diffusion cell permeation studies revealed that DNDI-0690 permeated poorly (<1%) into the skin lesion upon topical drug application (0.063% [wt/vol], 30 μl). In contrast,...