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Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient.
Adv Drug Deliv Rev. 2002 Nov 01; 54 Suppl 1:S57-75.AD

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.

Authors+Show Affiliations

Leiden-Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, P O Box 9502, 2300 RC, Leiden, The Netherlands. junginge@chem.leidenuniv.nl

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

12460716

Citation

Junginger, H E.. "Iontophoretic Delivery of Apomorphine: From In-vitro Modelling to the Parkinson Patient." Advanced Drug Delivery Reviews, vol. 54 Suppl 1, 2002, pp. S57-75.
Junginger HE. Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient. Adv Drug Deliv Rev. 2002;54 Suppl 1:S57-75.
Junginger, H. E. (2002). Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient. Advanced Drug Delivery Reviews, 54 Suppl 1, S57-75.
Junginger HE. Iontophoretic Delivery of Apomorphine: From In-vitro Modelling to the Parkinson Patient. Adv Drug Deliv Rev. 2002 Nov 1;54 Suppl 1:S57-75. PubMed PMID: 12460716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iontophoretic delivery of apomorphine: from in-vitro modelling to the Parkinson patient. A1 - Junginger,H E, PY - 2002/12/4/pubmed PY - 2003/5/23/medline PY - 2002/12/4/entrez SP - S57 EP - 75 JF - Advanced drug delivery reviews JO - Adv Drug Deliv Rev VL - 54 Suppl 1 N2 - 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. SN - 0169-409X UR - https://www.unboundmedicine.com/medline/citation/12460716/Iontophoretic_delivery_of_apomorphine:_from_in_vitro_modelling_to_the_Parkinson_patient_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169409X02001199 DB - PRIME DP - Unbound Medicine ER -