Van Bocxlaer, Katrien and Croft, Simon L (2021) Pharmacokinetics and pharmacodynamics in the treatment of cutaneous leishmaniasis - challenges and opportunities. RSC Medicinal Chemistry. pp. 472-482. ISSN 2632-8682
Abstract
Pharmacological efficacy is obtained when adequate concentrations of a potent drug reach the target site. In cutaneous leishmaniasis, a heterogeneous disease characterised by a variety of skin manifestations from simple nodules, skin discoloration, plaques to extensive disseminated forms, the parasites are found in the dermal layers of the skin. Treatment thus involves the release of the active compound from the formulation (administered either topically or systemically), it's permeation into the skin, accumulation by the local macrophages and further transport into the phagolysosome of the macrophage. The pharmacodynamic activity of a drug against the parasite is relatively straight forward to evaluate both in vivo and in vitro. The pharmacokinetic processes taking place inside the skin are more complex to elucidate due to the multi-lamellar structure of the skin, heterogeneous distribution of drugs within the tissue, the difficulty of accessing the site of infection complicating sampling and the lack of surrogate markers reflecting the activity of a drug in the skin. This review will discuss the difficulties encountered when investigating drug distribution, PK PD relationships and efficacy in the skin with a focus on cutaneous leishmaniasis treatment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This journal is © The Royal Society of Chemistry. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Environment and Geography (York) The University of York > Faculty of Sciences (York) > Stockholm Environment Institute at York (York) |
Depositing User: | Pure (York) |
Date Deposited: | 08 Aug 2024 09:20 |
Last Modified: | 21 Jan 2025 18:14 |
Published Version: | https://doi.org/10.1039/d0md00343c |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1039/d0md00343c |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215873 |