Evaluation of microdialysis as a tool for studying percutaneous drug absorption
Evaluation of microdialysis as a tool for studying percutaneous drug absorption
This thesis investigates the technique of cutaneous microdialysis as a means of exploring the factors that affect the absorption of topically applied drugs. Following a description of the factors affecting percutaneous absorption and methods used for studying percutaneous absorption the technique of microdialysis is described. The main advantage of cutaneous microdialysis is that it continuously samples from the dermal extracellular space in vivo and so enables a detailed pharmacokinetic profile to be built up of the drug under investigation under both normal and abnormal conditions. Using microdialysis to measure the dermal concentrations of the antiherpes drugs penciclovir (PCV) and acyclovir (ACV) following topical application, it was found that in their commercial preparations they are very poorly absorbed through normal skin. Therefore they represent suitable probes for investigating the different aspects of percutaneous absorption both in terms of the ‘penetrant’ and the barrier it has to cross.
The role of the stratum corneum barrier was investigated using tape stripping with transepidermal water loss measurement used as a measure of barrier impairment. PCV and ACV absorption were measured through different degrees of barrier impairment. Cutaneous blood flow was manipulated using noradrenaline as a vasoconstrictor and glyceryl trinitrate as a vasodilator to assess the effect of cutaneous blood flow on washing away percutaneously absorbed drug. Dermal levels of systemically absorbed PCV were compared with topically applied PCV. Finally microdialysis fibres have been uniquely used to continuously deliver muscarinic agonists to sweat glands to both clarify the physiology and pharmacology of eccrine sweat glands, and to investigate the absorption of PCV via skin appendages.
University of Southampton
Morgan, Caroline J
1901f7fd-b5c5-48ab-ba1a-71328c83ac72
2001
Morgan, Caroline J
1901f7fd-b5c5-48ab-ba1a-71328c83ac72
Morgan, Caroline J
(2001)
Evaluation of microdialysis as a tool for studying percutaneous drug absorption.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This thesis investigates the technique of cutaneous microdialysis as a means of exploring the factors that affect the absorption of topically applied drugs. Following a description of the factors affecting percutaneous absorption and methods used for studying percutaneous absorption the technique of microdialysis is described. The main advantage of cutaneous microdialysis is that it continuously samples from the dermal extracellular space in vivo and so enables a detailed pharmacokinetic profile to be built up of the drug under investigation under both normal and abnormal conditions. Using microdialysis to measure the dermal concentrations of the antiherpes drugs penciclovir (PCV) and acyclovir (ACV) following topical application, it was found that in their commercial preparations they are very poorly absorbed through normal skin. Therefore they represent suitable probes for investigating the different aspects of percutaneous absorption both in terms of the ‘penetrant’ and the barrier it has to cross.
The role of the stratum corneum barrier was investigated using tape stripping with transepidermal water loss measurement used as a measure of barrier impairment. PCV and ACV absorption were measured through different degrees of barrier impairment. Cutaneous blood flow was manipulated using noradrenaline as a vasoconstrictor and glyceryl trinitrate as a vasodilator to assess the effect of cutaneous blood flow on washing away percutaneously absorbed drug. Dermal levels of systemically absorbed PCV were compared with topically applied PCV. Finally microdialysis fibres have been uniquely used to continuously deliver muscarinic agonists to sweat glands to both clarify the physiology and pharmacology of eccrine sweat glands, and to investigate the absorption of PCV via skin appendages.
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Published date: 2001
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Local EPrints ID: 465813
URI: http://eprints.soton.ac.uk/id/eprint/465813
PURE UUID: f28b265c-ce53-49dd-9122-6fe86d5afbe7
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Date deposited: 05 Jul 2022 03:11
Last modified: 16 Mar 2024 20:23
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Author:
Caroline J Morgan
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