2026-07-06T08:10:31Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/275802026-07-02T00:15:38Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud author Chu, Wan-Yu author Singh, Om Prakash author Sundar, Shyam author Mondal, Dinesh author Pandey, Krishna author Das, Pradeep author Roseboom, Ignace C author Raja, Sheeraz author Torres Garcia, Ana Maria author Carrillo, Eugenia author Huitema, Alwin D R author Alves, Fabiana author Dorlo, Thomas P C funder Dutch Research Council (Holanda) funder Swedish Research Council 2026-07-01T09:06:52Z 2026-07-01T09:06:52Z 2026-02 Chu, W.-Y., Singh, O.P., Sundar, S., Mondal, D., Pandey, K., Das, P., Roseboom, I.C., Raja, S., Torres, A., Carrillo, E., Huitema, A.D.R., Alves, F. and Dorlo, T.P.C. (2026), Bidirectional Interaction Between Liposomal Amphotericin B Pharmacokinetics and Parasite Dynamics in Patients With Post-Kala-Azar Dermal Leishmaniasis: Potential Implications for Optimal Dosing. Clin Pharmacol Ther, 119: 437-446. https://doi.org/10.1002/cpt.70124 10.1002/cpt.70124 Clinical Pharmacology & Therapeutics 41288134 https://hdl.handle.net/20.500.12105/27580 Post-kala-azar dermal leishmaniasis (PKDL) involves a high macrophage burden in which the Leishmania parasites reside. Liposomal amphotericin B (LAmB) plays a key role in the treatment of PKDL. The mononuclear phagocyte system (MPS) is crucial in the distribution of liposomal drugs as well as the leishmaniasis pathophysiology. This study focused on characterizing the interaction between LAmB pharmacokinetics, the MPS, and parasite dynamics for optimal dosing of LAmB in PKDL. Clinical trial data from the Indian subcontinent, involving short-course LAmB administered alone or with miltefosine, were analyzed using nonlinear mixed-effects modeling. The pharmacokinetics of LAmB were best described by a two-compartment model with a saturable LAmB uptake by the MPS. The maximum MPS uptake capacity was modeled with a baseline component and an additional disease-related component relative to the parasite burden. As treatment progressed, MPS capacity decreased with declining parasite load, resulting in a median 54% increase in the systemic LAmB exposure (AUC) by the end of treatment. Simulations suggested that a similar parasite clearance could be achieved with a 50% lower total LAmB dose, supporting the potential efficacy of reduced dosing regimens. Combining LAmB and miltefosine further accelerated parasite clearance compared to LAmB alone. This study 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 management of PKDL and other dermal leishmaniases. eng Bidirectional Interaction Between Liposomal Amphotericin B Pharmacokinetics and Parasite Dynamics in Patients With Post-Kala-Azar Dermal Leishmaniasis: Potential Implications for Optimal Dosing. research article 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 URL https://repisalud.isciii.es/bitstreams/da5c06be-0a1c-4e8f-bd2c-59217506f3e5/download File MD5 b8babcbd09ec0e96f2f8c435b8aeb9d0 1525339 application/pdf BidirectionalInteractionBetweenLiposomal_2025.pdf URL https://repisalud.isciii.es/bitstreams/ced36dc8-a851-48c8-9030-c0d6e7d4cd79/download File MD5 a93493f396294f38ea3c4af871960c85 2569107 application/pdf Supplementary_BidirectionalInteractionBetweenLiposomal_2025.pdf URL https://repisalud.isciii.es/bitstreams/be7eaa2a-b742-41f4-81d6-46181340fb17/download File MD5 87358813c791693e8046137e60a92bea 1087541 application/zip Figures_BidirectionalInteractionBetweenLiposomal_2025.zip