Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach.

Miltefosine (MTS) is the only approved oral drug for treating leishmaniasis caused by intracellular parasites that localize in macrophages of the liver, spleen, skin, bone marrow, and lymph nodes. MTS is extensively distributed in tissues and has prolonged elimination half-lives due to its high plasma protein binding, slow metabolic clearance, and minimal urinary excretion. Thus, understanding and predicting the tissue distribution of MTS help assess therapeutic and toxicologic outcomes of MTS, especially in special populations, e.