Bidirectional interaction between liposomal amphotericin B pharmacokinetics and parasite dynamics in patients with post-kala-azar dermal leishmaniasis: Potential implications for optimal dosing

by Chu W-Y, Prakash Singh O, Sundar S, Mondal D, Pandey K, Das P, Roseboom IC, Raja S, Torres A, Carrillo E, Huitema ADR, Alves F, Dorlo TPC. Clinical Pharmacology & Therapeutics 2025. doi: 10.1002/cpt.70124

Summary: The authors of this study characterized the interaction between liposomal amphotericin B (LAmB) pharmacokinetics, the mononuclear phagocyte system, and parasite dynamics to determine optimal dosing of LAmB in post-kala-azar dermal leishmaniasis (PKDL). Clinical trial data from the Indian subcontinent, involving short-course LAmB administered alone or with miltefosine, were analyzed using nonlinear mixed-effects modeling. Simulations suggested similar parasite clearance could be achieved with a 50% lower total LAmB dose. Combining LAmB and miltefosine further accelerated parasite clearance compared to LAmB alone. This highlights the importance of understanding the bidirectional interactions between LAmB pharmacokinetics and parasite infection for interpreting systemic exposure and optimizing treatment approaches. If confirmed in clinical trials, reduced LAmB dosing strategies could enable more rational and cost-effective PKDL management.

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