by Palić S, Chu W-Y, Sundar S, Mondal D, Das P, Pandey K, Raja S, Rijal S, Roseboom IC, Hamadeh A, Malik PRV, Beijnen JH, Huitema ADR, Sjögren E, Alves F, Dorlo TPC. Journal of Antimicrobial Chemotherapy 2024, 79(7):1547–1554. doi: 10.1093/jac/dkae129
Summary: Current treatments for post-kala-azar dermal leishmaniasis (PKDL) are unsatisfactory, and the distribution of antileishmanial compounds within human skin is not well understood. The authors of this study investigated the skin distribution of miltefosine in patients with PKDL to better understand its pharmacokinetics at the target site. Fifty-two patients with PKDL were treated with liposomal amphotericin B (20 mg/kg) plus miltefosine (allometric dosing) for 21 days. Miltefosine concentrations were measured in plasma and skin, and a physiologically based pharmacokinetic (PBPK) model was developed to evaluate the distribution of miltefosine into the skin. This study provides the first accurate measurements of miltefosine penetration into the skin, demonstrating substantial exposure and prolonged retention. These findings support its use in cutaneous manifestations of leishmaniasis.
