In vitro metabolism, disposition, preclinical pharmacokinetics and prediction of human pharmacokinetics of DNDI-VL-2098, a potential oral treatment for Visceral Leishmaniasis
- Department for International Development
- 1 January 2014
- Document Type:
- Journal Article
- Martin, D., Mondal, S., Launay, D., Pinjari, J., Ramanathan, V., Chadrashekar, G., Gadekar, A., Harisudhan, T., Koiram, P., Moinuddin, A., Mukkavilli, R., Patel, B., Patel, J., Pothuri, L., Sengottuvelan, S., Vachharajani, N., and Verma, M.
The in vitro metabolism and in vivo pharmacokinetic (PK) properties of DNDI-VL-2098, a potential oral agent for Visceral Leishmaniasis (VL) were studied and used to predict its human pharmacokinetics. DNDI-VL-2098 showed a low solubility (10 μM) and was highly permeable (>200 nm/s) in the Caco-2 model. It was stable in vitro in liver microsomes and hepatocytes and no metabolite was detectable in circulating plasma from dosed animals suggesting very slow, if any, metabolism of the compound. DNDI-VL-2098 was moderate to highly bound to plasma proteins across the species tested (94–98%). DNDI-VL-2098 showed satisfactory PK properties in mouse, hamster, rat and dog with a low blood clearance (
Mukkavilli, R.; Pinjari, J.; Patel, B.; Sengottuvelan, S.; Mondal, S.; Gadekar, A.; Verma, M.; Patel, J.; Pothuri, L.; Chadrashekar, G.; Koiram, P.; Harisudhan, T.; Moinuddin, A.; Launay, D.; Vachharajani, N.; Ramanathan, V.; Martin, D. In vitro metabolism, disposition, preclinical pharmacokinetics and prediction of human pharmacokinetics of DNDI-VL-2098, a potential oral treatment for Visceral Leishmaniasis. European Journal of Pharmaceutical Sciences (2014) 65: 147-155. [DOI: 10.1016/j.ejps.2014.09.006]
Published: 1 January 2014
Document Type: Journal Article
Authors: Martin, D. Mondal, S. Launay, D. Pinjari, J. Ramanathan, V. Chadrashekar, G. Gadekar, A. Harisudhan, T. Koiram, P. Moinuddin, A. Mukkavilli, R. Patel, B. Patel, J. Pothuri, L. Sengottuvelan, S. Vachharajani, N. Verma, M.