Iontophoretic delivery of apomorphine II : An in vivo study in patients with Parkinson's disease
Transdermal transport rates of the dopamine agonist R-apomorphine were determined in patients with idiopathic Parkinson's disease (IPD). Apomorphine was applied by iontophoresis at two current densities. In ten patients apomorphine was applied passively for one hour. Thereafter, in the first fi...
Gespeichert in:
| Veröffentlicht in: | Pharmaceutical research 1997-12, Vol.14 (12), p.1804-1810 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1810 |
|---|---|
| container_issue | 12 |
| container_start_page | 1804 |
| container_title | Pharmaceutical research |
| container_volume | 14 |
| creator | VAN DER GEEST, R VAN LAAR, T GUBBENS-STIBBE, J. M BODDE, H. E DANHOF, M |
| description | Transdermal transport rates of the dopamine agonist R-apomorphine were determined in patients with idiopathic Parkinson's disease (IPD). Apomorphine was applied by iontophoresis at two current densities.
In ten patients apomorphine was applied passively for one hour. Thereafter, in the first five patients, a current density of 250 microA.cm-2 was applied for one hour and a current density of 375 microA.cm-2 in the second group. The individual pharmacokinetic parameters were obtained separately following a 15-minute zero-order intravenous infusion of 30 micrograms.kg-1. Skin resistance was measured during current delivery. Current-induced irritation was measured by Laser Doppler Flowmetry (LDF). The pharmacodynamics were quantified by a unilateral tapping score. Qualitative clinical improvements (decreased tremor, rigidity or cramp) were also recorded.
In all patients increasing plasma concentrations of R-apomorphine were found during the interval of current application. The maximum concentrations that were attained were related to the applied current density: 1.3 +/- 0.6 ng.ml-1 at 250 microA.cm-2 and 2.5 +/- 0.7 ng.ml-1 at 375 microA.cm-2. When the current was switched off all concentrations returned to baseline values in about 90 minutes. By mathematical deconvolution of the profiles it was shown that steady-state fluxes were reached within the one-hour interval of current driven transport Steady-state fluxes were calculated to be 69 +/- 30 nmol.cm-2.h-1 at 250 microA.cm-2 and 114 +/- 34 nmol.cm-2.h-1 at 375 microA.cm-2. Individual drug input rates were inversely related to the overall resistance. Significantly elevated LDF values were found after patch removal, indicating mild current induced erythema. Only subtherapeutic plasma concentrations were obtained in all patients except for one.
The results show that current-dependent delivery of apomorphine is possible in vivo at acceptable levels of skin irritation. Excellent correlation was found between the calculated in vivo transport rates and the rates that were previously obtained in vitro. |
| doi_str_mv | 10.1023/A:1012152401715 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_79537661</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>79537661</sourcerecordid><originalsourceid>FETCH-LOGICAL-c308t-276918105b8c5fcfd5b80648ead825e4694bd23df6d0ab294e9b2b547fa3d7913</originalsourceid><addsrcrecordid>eNpdkEtLxDAURoMoOj7WroQgoqtqnk0yu2HwURjQhYK7mjYpE-0kNWlH5t9bcXDh6t7LOXx8XABOMbrGiNCb2RQjTDAnDGGB-Q6YYC5ophB73QUTJAjLpGD4ABym9I4QklixfbCvGKcjnIC3Ivg-dMsQbe9qaGzr1jZuYGig7sIqxG7pvIVFAadw5qHzcO3WAaZ-MJufq9O9s75P8Mv1S_ik44fzKfirBI1LVid7DPYa3SZ7sp1H4OXu9nn-kC0e74v5bJHVFMk-IyJXWGLEK1nzpm7MuKCcSauNJNyyXLHKEGqa3CBdEcWsqkjFmWg0NUJhegQuf3O7GD4Hm_py5VJt21Z7G4ZUCsWpyPMf8fyf-B6G6MduJSEkl1KqfJTOttJQrawpu-hWOm7K7d9GfrHlOtW6baL2tUt_GsFYcITpNziAe10</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222688896</pqid></control><display><type>article</type><title>Iontophoretic delivery of apomorphine II : An in vivo study in patients with Parkinson's disease</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>VAN DER GEEST, R ; VAN LAAR, T ; GUBBENS-STIBBE, J. M ; BODDE, H. E ; DANHOF, M</creator><creatorcontrib>VAN DER GEEST, R ; VAN LAAR, T ; GUBBENS-STIBBE, J. M ; BODDE, H. E ; DANHOF, M</creatorcontrib><description>Transdermal transport rates of the dopamine agonist R-apomorphine were determined in patients with idiopathic Parkinson's disease (IPD). Apomorphine was applied by iontophoresis at two current densities.
In ten patients apomorphine was applied passively for one hour. Thereafter, in the first five patients, a current density of 250 microA.cm-2 was applied for one hour and a current density of 375 microA.cm-2 in the second group. The individual pharmacokinetic parameters were obtained separately following a 15-minute zero-order intravenous infusion of 30 micrograms.kg-1. Skin resistance was measured during current delivery. Current-induced irritation was measured by Laser Doppler Flowmetry (LDF). The pharmacodynamics were quantified by a unilateral tapping score. Qualitative clinical improvements (decreased tremor, rigidity or cramp) were also recorded.
In all patients increasing plasma concentrations of R-apomorphine were found during the interval of current application. The maximum concentrations that were attained were related to the applied current density: 1.3 +/- 0.6 ng.ml-1 at 250 microA.cm-2 and 2.5 +/- 0.7 ng.ml-1 at 375 microA.cm-2. When the current was switched off all concentrations returned to baseline values in about 90 minutes. By mathematical deconvolution of the profiles it was shown that steady-state fluxes were reached within the one-hour interval of current driven transport Steady-state fluxes were calculated to be 69 +/- 30 nmol.cm-2.h-1 at 250 microA.cm-2 and 114 +/- 34 nmol.cm-2.h-1 at 375 microA.cm-2. Individual drug input rates were inversely related to the overall resistance. Significantly elevated LDF values were found after patch removal, indicating mild current induced erythema. Only subtherapeutic plasma concentrations were obtained in all patients except for one.
The results show that current-dependent delivery of apomorphine is possible in vivo at acceptable levels of skin irritation. Excellent correlation was found between the calculated in vivo transport rates and the rates that were previously obtained in vitro.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1012152401715</identifier><identifier>PMID: 9453072</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Administration, Cutaneous ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Antiparkinson Agents - administration & dosage ; Antiparkinson Agents - blood ; Antiparkinson Agents - pharmacokinetics ; Apomorphine - administration & dosage ; Apomorphine - blood ; Apomorphine - pharmacokinetics ; Biological and medical sciences ; Cross-Over Studies ; Female ; Humans ; Iontophoresis ; Male ; Medical sciences ; Metabolic Clearance Rate ; Middle Aged ; Neuropharmacology ; Parkinson Disease - blood ; Parkinson Disease - metabolism ; Pharmacology. Drug treatments ; Skin - innervation ; Skin - metabolism</subject><ispartof>Pharmaceutical research, 1997-12, Vol.14 (12), p.1804-1810</ispartof><rights>1998 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Dec 1997</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c308t-276918105b8c5fcfd5b80648ead825e4694bd23df6d0ab294e9b2b547fa3d7913</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2117501$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9453072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VAN DER GEEST, R</creatorcontrib><creatorcontrib>VAN LAAR, T</creatorcontrib><creatorcontrib>GUBBENS-STIBBE, J. M</creatorcontrib><creatorcontrib>BODDE, H. E</creatorcontrib><creatorcontrib>DANHOF, M</creatorcontrib><title>Iontophoretic delivery of apomorphine II : An in vivo study in patients with Parkinson's disease</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Transdermal transport rates of the dopamine agonist R-apomorphine were determined in patients with idiopathic Parkinson's disease (IPD). Apomorphine was applied by iontophoresis at two current densities.
In ten patients apomorphine was applied passively for one hour. Thereafter, in the first five patients, a current density of 250 microA.cm-2 was applied for one hour and a current density of 375 microA.cm-2 in the second group. The individual pharmacokinetic parameters were obtained separately following a 15-minute zero-order intravenous infusion of 30 micrograms.kg-1. Skin resistance was measured during current delivery. Current-induced irritation was measured by Laser Doppler Flowmetry (LDF). The pharmacodynamics were quantified by a unilateral tapping score. Qualitative clinical improvements (decreased tremor, rigidity or cramp) were also recorded.
In all patients increasing plasma concentrations of R-apomorphine were found during the interval of current application. The maximum concentrations that were attained were related to the applied current density: 1.3 +/- 0.6 ng.ml-1 at 250 microA.cm-2 and 2.5 +/- 0.7 ng.ml-1 at 375 microA.cm-2. When the current was switched off all concentrations returned to baseline values in about 90 minutes. By mathematical deconvolution of the profiles it was shown that steady-state fluxes were reached within the one-hour interval of current driven transport Steady-state fluxes were calculated to be 69 +/- 30 nmol.cm-2.h-1 at 250 microA.cm-2 and 114 +/- 34 nmol.cm-2.h-1 at 375 microA.cm-2. Individual drug input rates were inversely related to the overall resistance. Significantly elevated LDF values were found after patch removal, indicating mild current induced erythema. Only subtherapeutic plasma concentrations were obtained in all patients except for one.
The results show that current-dependent delivery of apomorphine is possible in vivo at acceptable levels of skin irritation. Excellent correlation was found between the calculated in vivo transport rates and the rates that were previously obtained in vitro.</description><subject>Administration, Cutaneous</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Antiparkinson Agents - administration & dosage</subject><subject>Antiparkinson Agents - blood</subject><subject>Antiparkinson Agents - pharmacokinetics</subject><subject>Apomorphine - administration & dosage</subject><subject>Apomorphine - blood</subject><subject>Apomorphine - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Cross-Over Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Iontophoresis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic Clearance Rate</subject><subject>Middle Aged</subject><subject>Neuropharmacology</subject><subject>Parkinson Disease - blood</subject><subject>Parkinson Disease - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Skin - innervation</subject><subject>Skin - metabolism</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpdkEtLxDAURoMoOj7WroQgoqtqnk0yu2HwURjQhYK7mjYpE-0kNWlH5t9bcXDh6t7LOXx8XABOMbrGiNCb2RQjTDAnDGGB-Q6YYC5ophB73QUTJAjLpGD4ABym9I4QklixfbCvGKcjnIC3Ivg-dMsQbe9qaGzr1jZuYGig7sIqxG7pvIVFAadw5qHzcO3WAaZ-MJufq9O9s75P8Mv1S_ik44fzKfirBI1LVid7DPYa3SZ7sp1H4OXu9nn-kC0e74v5bJHVFMk-IyJXWGLEK1nzpm7MuKCcSauNJNyyXLHKEGqa3CBdEcWsqkjFmWg0NUJhegQuf3O7GD4Hm_py5VJt21Z7G4ZUCsWpyPMf8fyf-B6G6MduJSEkl1KqfJTOttJQrawpu-hWOm7K7d9GfrHlOtW6baL2tUt_GsFYcITpNziAe10</recordid><startdate>19971201</startdate><enddate>19971201</enddate><creator>VAN DER GEEST, R</creator><creator>VAN LAAR, T</creator><creator>GUBBENS-STIBBE, J. M</creator><creator>BODDE, H. E</creator><creator>DANHOF, M</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>19971201</creationdate><title>Iontophoretic delivery of apomorphine II : An in vivo study in patients with Parkinson's disease</title><author>VAN DER GEEST, R ; VAN LAAR, T ; GUBBENS-STIBBE, J. M ; BODDE, H. E ; DANHOF, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c308t-276918105b8c5fcfd5b80648ead825e4694bd23df6d0ab294e9b2b547fa3d7913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Administration, Cutaneous</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Antiparkinson Agents - administration & dosage</topic><topic>Antiparkinson Agents - blood</topic><topic>Antiparkinson Agents - pharmacokinetics</topic><topic>Apomorphine - administration & dosage</topic><topic>Apomorphine - blood</topic><topic>Apomorphine - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Cross-Over Studies</topic><topic>Female</topic><topic>Humans</topic><topic>Iontophoresis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic Clearance Rate</topic><topic>Middle Aged</topic><topic>Neuropharmacology</topic><topic>Parkinson Disease - blood</topic><topic>Parkinson Disease - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Skin - innervation</topic><topic>Skin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VAN DER GEEST, R</creatorcontrib><creatorcontrib>VAN LAAR, T</creatorcontrib><creatorcontrib>GUBBENS-STIBBE, J. M</creatorcontrib><creatorcontrib>BODDE, H. E</creatorcontrib><creatorcontrib>DANHOF, M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VAN DER GEEST, R</au><au>VAN LAAR, T</au><au>GUBBENS-STIBBE, J. M</au><au>BODDE, H. E</au><au>DANHOF, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Iontophoretic delivery of apomorphine II : An in vivo study in patients with Parkinson's disease</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>1997-12-01</date><risdate>1997</risdate><volume>14</volume><issue>12</issue><spage>1804</spage><epage>1810</epage><pages>1804-1810</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Transdermal transport rates of the dopamine agonist R-apomorphine were determined in patients with idiopathic Parkinson's disease (IPD). Apomorphine was applied by iontophoresis at two current densities.
In ten patients apomorphine was applied passively for one hour. Thereafter, in the first five patients, a current density of 250 microA.cm-2 was applied for one hour and a current density of 375 microA.cm-2 in the second group. The individual pharmacokinetic parameters were obtained separately following a 15-minute zero-order intravenous infusion of 30 micrograms.kg-1. Skin resistance was measured during current delivery. Current-induced irritation was measured by Laser Doppler Flowmetry (LDF). The pharmacodynamics were quantified by a unilateral tapping score. Qualitative clinical improvements (decreased tremor, rigidity or cramp) were also recorded.
In all patients increasing plasma concentrations of R-apomorphine were found during the interval of current application. The maximum concentrations that were attained were related to the applied current density: 1.3 +/- 0.6 ng.ml-1 at 250 microA.cm-2 and 2.5 +/- 0.7 ng.ml-1 at 375 microA.cm-2. When the current was switched off all concentrations returned to baseline values in about 90 minutes. By mathematical deconvolution of the profiles it was shown that steady-state fluxes were reached within the one-hour interval of current driven transport Steady-state fluxes were calculated to be 69 +/- 30 nmol.cm-2.h-1 at 250 microA.cm-2 and 114 +/- 34 nmol.cm-2.h-1 at 375 microA.cm-2. Individual drug input rates were inversely related to the overall resistance. Significantly elevated LDF values were found after patch removal, indicating mild current induced erythema. Only subtherapeutic plasma concentrations were obtained in all patients except for one.
The results show that current-dependent delivery of apomorphine is possible in vivo at acceptable levels of skin irritation. Excellent correlation was found between the calculated in vivo transport rates and the rates that were previously obtained in vitro.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>9453072</pmid><doi>10.1023/A:1012152401715</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 1997-12, Vol.14 (12), p.1804-1810 |
| issn | 0724-8741 1573-904X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79537661 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Administration, Cutaneous Anticonvulsants. Antiepileptics. Antiparkinson agents Antiparkinson Agents - administration & dosage Antiparkinson Agents - blood Antiparkinson Agents - pharmacokinetics Apomorphine - administration & dosage Apomorphine - blood Apomorphine - pharmacokinetics Biological and medical sciences Cross-Over Studies Female Humans Iontophoresis Male Medical sciences Metabolic Clearance Rate Middle Aged Neuropharmacology Parkinson Disease - blood Parkinson Disease - metabolism Pharmacology. Drug treatments Skin - innervation Skin - metabolism |
| title | Iontophoretic delivery of apomorphine II : An in vivo study in patients with Parkinson's disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T02%3A27%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Iontophoretic%20delivery%20of%20apomorphine%20II%20:%20An%20in%20vivo%20study%20in%20patients%20with%20Parkinson's%20disease&rft.jtitle=Pharmaceutical%20research&rft.au=VAN%20DER%20GEEST,%20R&rft.date=1997-12-01&rft.volume=14&rft.issue=12&rft.spage=1804&rft.epage=1810&rft.pages=1804-1810&rft.issn=0724-8741&rft.eissn=1573-904X&rft.coden=PHREEB&rft_id=info:doi/10.1023/A:1012152401715&rft_dat=%3Cproquest_pubme%3E79537661%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222688896&rft_id=info:pmid/9453072&rfr_iscdi=true |