Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient
Identifieur interne : 003507 ( Main/Exploration ); précédent : 003506; suivant : 003508Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient
Auteurs : H. E. Junginger [Pays-Bas]Source :
- Advanced drug delivery reviews [ 0169-409X ] ; 2002.
Descripteurs français
- Pascal (Inist)
- Apomorphine, Stimulant dopaminergique, Système administration, Ionophorèse, Peau, Article synthèse, Parkinson maladie, Système transdermique, Technologie pharmaceutique, Irritation, Toxicité, Diffusion, Perméation, Transport biologique, Pharmacocinétique, Activité biologique, Absorption, Patch, Promoteur absorption.
English descriptors
- KwdEn :
Abstract
Apomorphine is a mixed dopamine D1/D2 receptor agonist which is potentially useful in the treatment of Parkinson's disease. The delivery of apomorphine is however complicated because it is not absorbed orally and other delivery routes with the exception of the intravenous route seem to fail. The most interesting route for controlled delivery of apomorphine is transdermal iontophoresis because this could enable the Parkinson patient to directly control the needed amount of apomorphine by increasing or decreasing the drug input in order to achieve optimal drug therapy ('on-demand') with a minimum of toxic side effects. The typical features of Parkinson's disease could be used to monitor the needed drug input and even more elegantly by means of suitable chip sensors which are able to directly measure bradykinesia, akinesia and/or tremor and to regulate in such a way the drug input. Such a chip-controlled iontophoretic system would be the first closed-loop system monitoring not pharmacokinetic data (blood levels) but more importantly externally measurable pharmacodynamic effects of Parkinson's disease. This scenario is more feasible as skin irritation and toxicity studies have proven that iontophoresis is a safe route of treatment. This review describes the basics of iontophoresis and the development of a transdermal iontophoretic delivery system on the basis of integrated pharmacokinetic/pharmacodynamic (PK/PD) investigations in patients with idiopathic Parkinson's disease. Transdermal iontophoretic transport of apomorphine was studied both in vitro with human stratum corneum using a newly developed iontophoretic continuous flow-through transport cell and in vivo in a first exploratory study in patients with Parkinson's disease. These studies showed that the delivery of apomorphine is feasible and furthermore the rate of delivery can be controlled by variation of the current densities. Additionally the pretreatment of the skin either with a mono-surfactant or a vesicular suspension of elastic liquid-state vesicles may be useful to further increase the apomorphine flux across the skin in combination with iontophoresis.
Affiliations:
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Le document en format XML
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Box 9502</s1><s2>2300 RC Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RC Leiden</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">03-0114155</idno><date when="2002">2002</date><idno type="stanalyst">PASCAL 03-0114155 INIST</idno><idno type="RBID">Pascal:03-0114155</idno><idno type="wicri:Area/PascalFrancis/Corpus">000F86</idno><idno type="wicri:Area/PascalFrancis/Curation">000448</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000F30</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000F30</idno><idno type="wicri:doubleKey">0169-409X:2002:Junginger H:iontophoretic:delivery:of</idno><idno type="wicri:Area/Main/Merge">003A45</idno><idno type="wicri:Area/Main/Curation">003507</idno><idno type="wicri:Area/Main/Exploration">003507</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient</title><author><name sortKey="Junginger, H E" sort="Junginger, H E" uniqKey="Junginger H" first="H. E." last="Junginger">H. E. Junginger</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Leiden-Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, P.O. Box 9502</s1><s2>2300 RC Leiden</s2><s3>NLD</s3><sZ>1 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>2300 RC Leiden</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Advanced drug delivery reviews</title><title level="j" type="abbreviated">Adv. drug deliv. rev.</title><idno type="ISSN">0169-409X</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Advanced drug delivery reviews</title><title level="j" type="abbreviated">Adv. drug deliv. rev.</title><idno type="ISSN">0169-409X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Absorption</term><term>Absorption enhancer</term><term>Biological activity</term><term>Biological transport</term><term>Delivery system</term><term>Diffusion</term><term>Dopamine agonist</term><term>Iontophoresis</term><term>Irritation</term><term>Parkinson disease</term><term>Patch</term><term>Permeation</term><term>Pharmaceutical technology</term><term>Pharmacokinetics</term><term>Review</term><term>Skin</term><term>Toxicity</term><term>Transdermal system</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Apomorphine</term><term>Stimulant dopaminergique</term><term>Système administration</term><term>Ionophorèse</term><term>Peau</term><term>Article synthèse</term><term>Parkinson maladie</term><term>Système transdermique</term><term>Technologie pharmaceutique</term><term>Irritation</term><term>Toxicité</term><term>Diffusion</term><term>Perméation</term><term>Transport biologique</term><term>Pharmacocinétique</term><term>Activité biologique</term><term>Absorption</term><term>Patch</term><term>Promoteur absorption</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Apomorphine is a mixed dopamine D<sub>1</sub>/D<sub>2</sub> receptor agonist which is potentially useful in the treatment of Parkinson's disease. The delivery of apomorphine is however complicated because it is not absorbed orally and other delivery routes with the exception of the intravenous route seem to fail. The most interesting route for controlled delivery of apomorphine is transdermal iontophoresis because this could enable the Parkinson patient to directly control the needed amount of apomorphine by increasing or decreasing the drug input in order to achieve optimal drug therapy ('on-demand') with a minimum of toxic side effects. The typical features of Parkinson's disease could be used to monitor the needed drug input and even more elegantly by means of suitable chip sensors which are able to directly measure bradykinesia, akinesia and/or tremor and to regulate in such a way the drug input. Such a chip-controlled iontophoretic system would be the first closed-loop system monitoring not pharmacokinetic data (blood levels) but more importantly externally measurable pharmacodynamic effects of Parkinson's disease. This scenario is more feasible as skin irritation and toxicity studies have proven that iontophoresis is a safe route of treatment. This review describes the basics of iontophoresis and the development of a transdermal iontophoretic delivery system on the basis of integrated pharmacokinetic/pharmacodynamic (PK/PD) investigations in patients with idiopathic Parkinson's disease. Transdermal iontophoretic transport of apomorphine was studied both in vitro with human stratum corneum using a newly developed iontophoretic continuous flow-through transport cell and in vivo in a first exploratory study in patients with Parkinson's disease. These studies showed that the delivery of apomorphine is feasible and furthermore the rate of delivery can be controlled by variation of the current densities. Additionally the pretreatment of the skin either with a mono-surfactant or a vesicular suspension of elastic liquid-state vesicles may be useful to further increase the apomorphine flux across the skin in combination with iontophoresis.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country></list><tree><country name="Pays-Bas"><noRegion><name sortKey="Junginger, H E" sort="Junginger, H E" uniqKey="Junginger H" first="H. E." last="Junginger">H. E. Junginger</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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