Iontophoresis

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Jeanluc Cracowski - One of the best experts on this subject based on the ideXlab platform.

  • treprostinil Iontophoresis improves digital blood flow during local cooling in systemic sclerosis
    Microcirculation, 2016
    Co-Authors: Florence Gaillardbigot, S Blaise, Matthieu Roustit, Claire Cracowski, C Seinturier, B Imbert, P Carpentier, Jeanluc Cracowski
    Abstract:

    Introduction Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil Iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling. Methods Eleven patients with limited cutaneous SSc underwent a double-blinded Iontophoresis of treprostinil (2.56 × 10−4 M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8°C, and skin blood flow was recorded continuously using LSCI. Results During the local cooling, CVC was significantly higher at the treprostinil site than at the placebo site and remained higher 30 minutes after the test. Conclusions In patients with SSc, digital treprostinil Iontophoresis shifts skin blood flow upward during local cooling of the hand and during the initial rewarming phase. Digital treprostinil Iontophoresis should now be tested in larger scale studies.

  • trials and tribulations of skin Iontophoresis in therapeutics
    British Journal of Clinical Pharmacology, 2014
    Co-Authors: S Blaise, Matthieu Roustit, Jeanluc Cracowski
    Abstract:

    Iontophoresis is a method of non-invasive transdermal drug delivery based on the transfer of charged molecules using a low-intensity electric current. Both local and systemic administration are possible; however, the skin pharmacokinetics of iontophoretically delivered drugs is complex and difficult to anticipate. The unquestionable theoretical advantages of the technique make it attractive in several potential applications. After a brief review of the factors influencing Iontophoresis, we detail the current applications of Iontophoresis in therapeutics and the main potential applications under investigation, including systemic and topical drugs and focusing on the treatment of scleroderma-related ulcerations. Finally, we address the issue of safety, which could be a limitation to the routine clinical use of Iontophoresis.

  • cathodal Iontophoresis of treprostinil and iloprost induces a sustained increase in cutaneous flux in rats
    British Journal of Pharmacology, 2011
    Co-Authors: S Blaise, Matthieu Roustit, Jeanluc Cracowski, Claire Millet, Christophe Ribuot, J Boutonnat
    Abstract:

    BACKGROUND AND PURPOSE The treatment of scleroderma-related digital ulcers is still a therapeutic challenge. The most effective drugs are prostacyclin analogues. However, their usage is limited to an intravenous route of administration and by their frequent side effects. The objective of this study was to test whether treprostinil, iloprost and epoprostenol can induce sustained vasodilatation in rats when delivered locally using cutaneous Iontophoresis. EXPERIMENTAL APPROACH Treprostinil, iloprost and epoprostenol were delivered by cathodal and anodal Iontophoresis onto the hindquarters of anaesthesized rats (n= 8 for each group). Skin blood flow was quantified using laser Doppler imaging and cutaneous tolerance was assessed from day 0 to day 3. KEY RESULTS Cathodal but not anodal Iontophoresis of treprostinil (6.4 mM), iloprost (0.2 mM) and epoprostenol (1.4 mM) induced a significant and sustained increase in cutaneous blood flow. The effects of treprostinil and iloprost were significantly different from those of treprostinil vehicle. Only weak effects were observed when both drugs were applied locally without current. Skin resistance was unchanged in areas treated with prostacyclin analogues. Finally, skin tolerance was good, with no evidence of epidermal damage. CONCLUSIONS AND IMPLICATIONS Cathodal Iontophoresis of treprostinil and iloprost increases cutaneous blood flow with a good local tolerance. The effects of cathodal Iontophoresis of these drugs should be investigated in humans, as they could have potential as new local therapies for digital ulcers in patients with scleroderma.

  • oral sildenafil increases skin hyperaemia induced by Iontophoresis of sodium nitroprusside in healthy volunteers
    British Journal of Pharmacology, 2010
    Co-Authors: S Blaise, Marcin Hellmann, Matthieu Roustit, S Isnard, Jeanluc Cracowski
    Abstract:

    Background and purpose:  Sildenafil, a specific inhibitor of phosphodiesterase 5A (PDE5A), is currently tested as a treatment for severe Raynaud's phenomenon. Here, we tested whether sildenafil, alone or combined with local sodium nitroprusside (SNP) delivered through skin Iontophoresis, increased forearm cutaneous blood conductance in healthy volunteers, and to assess how well this combination was tolerated. Experimental approach:  Ten healthy volunteers were enrolled. Variations in cutaneous vascular conductance (CVC) following oral administration of 50 or 100 mg of sildenafil with or without SNP Iontophoresis were expressed as a percentage of maximal CVC, and were monitored using laser Doppler imaging. SNP Iontophoresis was performed on the ventral surface of the forearm, 1 h after application of lidocaine/prilocaine cream. Key results:  Sildenafil at 100 mg, but not 50 mg, increased overall responses (area under the curve) (44%) and peak responses (29%) to SNP Iontophoresis. Sildenafil at 100 mg, but not 50 mg, increased baseline CVC (75%). Incidence of headache was not changed when SNP Iontophoresis was combined with sildenafil. One episode of symptomatic arterial hypotension occurred in a volunteer given 50 mg sildenafil, 30 min after the beginning of SNP Iontophoresis. Conclusions and implications:  Oral sildenafil at 100 mg potentiated local skin hyperaemia induced by SNP Iontophoresis, with no increased incidence of headaches. The combination of oral specific PDE5A inhibitor and nitrates administered through skin Iontophoresis deserves further investigation in diseases such as severe Raynaud's phenomenon, with particular attention to the incidence of arterial hypotension.

S Blaise - One of the best experts on this subject based on the ideXlab platform.

  • treprostinil Iontophoresis improves digital blood flow during local cooling in systemic sclerosis
    Microcirculation, 2016
    Co-Authors: Florence Gaillardbigot, S Blaise, Matthieu Roustit, Claire Cracowski, C Seinturier, B Imbert, P Carpentier, Jeanluc Cracowski
    Abstract:

    Introduction Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil Iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling. Methods Eleven patients with limited cutaneous SSc underwent a double-blinded Iontophoresis of treprostinil (2.56 × 10−4 M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8°C, and skin blood flow was recorded continuously using LSCI. Results During the local cooling, CVC was significantly higher at the treprostinil site than at the placebo site and remained higher 30 minutes after the test. Conclusions In patients with SSc, digital treprostinil Iontophoresis shifts skin blood flow upward during local cooling of the hand and during the initial rewarming phase. Digital treprostinil Iontophoresis should now be tested in larger scale studies.

  • trials and tribulations of skin Iontophoresis in therapeutics
    British Journal of Clinical Pharmacology, 2014
    Co-Authors: S Blaise, Matthieu Roustit, Jeanluc Cracowski
    Abstract:

    Iontophoresis is a method of non-invasive transdermal drug delivery based on the transfer of charged molecules using a low-intensity electric current. Both local and systemic administration are possible; however, the skin pharmacokinetics of iontophoretically delivered drugs is complex and difficult to anticipate. The unquestionable theoretical advantages of the technique make it attractive in several potential applications. After a brief review of the factors influencing Iontophoresis, we detail the current applications of Iontophoresis in therapeutics and the main potential applications under investigation, including systemic and topical drugs and focusing on the treatment of scleroderma-related ulcerations. Finally, we address the issue of safety, which could be a limitation to the routine clinical use of Iontophoresis.

  • cathodal Iontophoresis of treprostinil and iloprost induces a sustained increase in cutaneous flux in rats
    British Journal of Pharmacology, 2011
    Co-Authors: S Blaise, Matthieu Roustit, Jeanluc Cracowski, Claire Millet, Christophe Ribuot, J Boutonnat
    Abstract:

    BACKGROUND AND PURPOSE The treatment of scleroderma-related digital ulcers is still a therapeutic challenge. The most effective drugs are prostacyclin analogues. However, their usage is limited to an intravenous route of administration and by their frequent side effects. The objective of this study was to test whether treprostinil, iloprost and epoprostenol can induce sustained vasodilatation in rats when delivered locally using cutaneous Iontophoresis. EXPERIMENTAL APPROACH Treprostinil, iloprost and epoprostenol were delivered by cathodal and anodal Iontophoresis onto the hindquarters of anaesthesized rats (n= 8 for each group). Skin blood flow was quantified using laser Doppler imaging and cutaneous tolerance was assessed from day 0 to day 3. KEY RESULTS Cathodal but not anodal Iontophoresis of treprostinil (6.4 mM), iloprost (0.2 mM) and epoprostenol (1.4 mM) induced a significant and sustained increase in cutaneous blood flow. The effects of treprostinil and iloprost were significantly different from those of treprostinil vehicle. Only weak effects were observed when both drugs were applied locally without current. Skin resistance was unchanged in areas treated with prostacyclin analogues. Finally, skin tolerance was good, with no evidence of epidermal damage. CONCLUSIONS AND IMPLICATIONS Cathodal Iontophoresis of treprostinil and iloprost increases cutaneous blood flow with a good local tolerance. The effects of cathodal Iontophoresis of these drugs should be investigated in humans, as they could have potential as new local therapies for digital ulcers in patients with scleroderma.

  • oral sildenafil increases skin hyperaemia induced by Iontophoresis of sodium nitroprusside in healthy volunteers
    British Journal of Pharmacology, 2010
    Co-Authors: S Blaise, Marcin Hellmann, Matthieu Roustit, S Isnard, Jeanluc Cracowski
    Abstract:

    Background and purpose:  Sildenafil, a specific inhibitor of phosphodiesterase 5A (PDE5A), is currently tested as a treatment for severe Raynaud's phenomenon. Here, we tested whether sildenafil, alone or combined with local sodium nitroprusside (SNP) delivered through skin Iontophoresis, increased forearm cutaneous blood conductance in healthy volunteers, and to assess how well this combination was tolerated. Experimental approach:  Ten healthy volunteers were enrolled. Variations in cutaneous vascular conductance (CVC) following oral administration of 50 or 100 mg of sildenafil with or without SNP Iontophoresis were expressed as a percentage of maximal CVC, and were monitored using laser Doppler imaging. SNP Iontophoresis was performed on the ventral surface of the forearm, 1 h after application of lidocaine/prilocaine cream. Key results:  Sildenafil at 100 mg, but not 50 mg, increased overall responses (area under the curve) (44%) and peak responses (29%) to SNP Iontophoresis. Sildenafil at 100 mg, but not 50 mg, increased baseline CVC (75%). Incidence of headache was not changed when SNP Iontophoresis was combined with sildenafil. One episode of symptomatic arterial hypotension occurred in a volunteer given 50 mg sildenafil, 30 min after the beginning of SNP Iontophoresis. Conclusions and implications:  Oral sildenafil at 100 mg potentiated local skin hyperaemia induced by SNP Iontophoresis, with no increased incidence of headaches. The combination of oral specific PDE5A inhibitor and nitrates administered through skin Iontophoresis deserves further investigation in diseases such as severe Raynaud's phenomenon, with particular attention to the incidence of arterial hypotension.

Matthieu Roustit - One of the best experts on this subject based on the ideXlab platform.

  • assessing cutaneous microvascular function with Iontophoresis avoiding non specific vasodilation
    Microvascular Research, 2017
    Co-Authors: Jordan Loader, Matthieu Roustit, Frances Taylor, Richard J Macisaac, Simon Stewart, Christian Lorenzen, Guillaume Walther
    Abstract:

    Abstract Aim Iontophoresis of vasoactive agents is commonly used to assess cutaneous microvascular reactivity. However, it is known that Iontophoresis can be limited by confounding non-specific vasodilatory effects. Despite this, there is still no standardization of protocols or data expression. Therefore, this study evaluated commonly used protocols of Iontophoresis by assessing each for evidence of non-specific vasodilatory effects and examined the reproducibility of those protocols that are free of non-specific responses. Methods Twelve healthy participants were administered doses of acetylcholine (ACh) 1–2% and sodium nitroprusside (SNP) 1%, diluted in sodium chloride 0.9% or deionized water, and insulin 100 U/mL in a sterile diluent using Iontophoresis coupled with laser speckle contrast imaging (LSCI). Increases in blood flux at a control electrode, containing the diluent only, indicated a non-specific response. Reproducibility of Iontophoresis protocols that were free of non-specific vasodilatory effects were subsequently compared to that of post-occlusive reactive hyperemia (PORH), used as a standard, in 20 healthy participants. Results Iontophoresis of ACh or SNP in sodium choloride (0.02 mA for 200 and 400 s, respectively) and ACh in deionized water (0.1 mA for 30 s) mediated the least non-specific vasodilatory effects. Microvascular responses to insulin were mediated mainly by non-specific effects. Compared to PORH, the intraday and interday reproducibility for Iontophoresis of ACh and SNP (0.02 mA for 200 and 400 s, respectively) with LSCI was weaker, but still deemed good to excellent when data was expressed, in perfusion units or cutaneous vascular conductance, as the absolute peak blood flux response to the vascular reactivity test or as the change in blood flux between peak and baseline values. Conclusion This study provides updated recommendations for assessing cutaneous microvascular function with Iontophoresis.

  • treprostinil Iontophoresis improves digital blood flow during local cooling in systemic sclerosis
    Microcirculation, 2016
    Co-Authors: Florence Gaillardbigot, S Blaise, Matthieu Roustit, Claire Cracowski, C Seinturier, B Imbert, P Carpentier, Jeanluc Cracowski
    Abstract:

    Introduction Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil Iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling. Methods Eleven patients with limited cutaneous SSc underwent a double-blinded Iontophoresis of treprostinil (2.56 × 10−4 M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8°C, and skin blood flow was recorded continuously using LSCI. Results During the local cooling, CVC was significantly higher at the treprostinil site than at the placebo site and remained higher 30 minutes after the test. Conclusions In patients with SSc, digital treprostinil Iontophoresis shifts skin blood flow upward during local cooling of the hand and during the initial rewarming phase. Digital treprostinil Iontophoresis should now be tested in larger scale studies.

  • trials and tribulations of skin Iontophoresis in therapeutics
    British Journal of Clinical Pharmacology, 2014
    Co-Authors: S Blaise, Matthieu Roustit, Jeanluc Cracowski
    Abstract:

    Iontophoresis is a method of non-invasive transdermal drug delivery based on the transfer of charged molecules using a low-intensity electric current. Both local and systemic administration are possible; however, the skin pharmacokinetics of iontophoretically delivered drugs is complex and difficult to anticipate. The unquestionable theoretical advantages of the technique make it attractive in several potential applications. After a brief review of the factors influencing Iontophoresis, we detail the current applications of Iontophoresis in therapeutics and the main potential applications under investigation, including systemic and topical drugs and focusing on the treatment of scleroderma-related ulcerations. Finally, we address the issue of safety, which could be a limitation to the routine clinical use of Iontophoresis.

  • cathodal Iontophoresis of treprostinil and iloprost induces a sustained increase in cutaneous flux in rats
    British Journal of Pharmacology, 2011
    Co-Authors: S Blaise, Matthieu Roustit, Jeanluc Cracowski, Claire Millet, Christophe Ribuot, J Boutonnat
    Abstract:

    BACKGROUND AND PURPOSE The treatment of scleroderma-related digital ulcers is still a therapeutic challenge. The most effective drugs are prostacyclin analogues. However, their usage is limited to an intravenous route of administration and by their frequent side effects. The objective of this study was to test whether treprostinil, iloprost and epoprostenol can induce sustained vasodilatation in rats when delivered locally using cutaneous Iontophoresis. EXPERIMENTAL APPROACH Treprostinil, iloprost and epoprostenol were delivered by cathodal and anodal Iontophoresis onto the hindquarters of anaesthesized rats (n= 8 for each group). Skin blood flow was quantified using laser Doppler imaging and cutaneous tolerance was assessed from day 0 to day 3. KEY RESULTS Cathodal but not anodal Iontophoresis of treprostinil (6.4 mM), iloprost (0.2 mM) and epoprostenol (1.4 mM) induced a significant and sustained increase in cutaneous blood flow. The effects of treprostinil and iloprost were significantly different from those of treprostinil vehicle. Only weak effects were observed when both drugs were applied locally without current. Skin resistance was unchanged in areas treated with prostacyclin analogues. Finally, skin tolerance was good, with no evidence of epidermal damage. CONCLUSIONS AND IMPLICATIONS Cathodal Iontophoresis of treprostinil and iloprost increases cutaneous blood flow with a good local tolerance. The effects of cathodal Iontophoresis of these drugs should be investigated in humans, as they could have potential as new local therapies for digital ulcers in patients with scleroderma.

  • oral sildenafil increases skin hyperaemia induced by Iontophoresis of sodium nitroprusside in healthy volunteers
    British Journal of Pharmacology, 2010
    Co-Authors: S Blaise, Marcin Hellmann, Matthieu Roustit, S Isnard, Jeanluc Cracowski
    Abstract:

    Background and purpose:  Sildenafil, a specific inhibitor of phosphodiesterase 5A (PDE5A), is currently tested as a treatment for severe Raynaud's phenomenon. Here, we tested whether sildenafil, alone or combined with local sodium nitroprusside (SNP) delivered through skin Iontophoresis, increased forearm cutaneous blood conductance in healthy volunteers, and to assess how well this combination was tolerated. Experimental approach:  Ten healthy volunteers were enrolled. Variations in cutaneous vascular conductance (CVC) following oral administration of 50 or 100 mg of sildenafil with or without SNP Iontophoresis were expressed as a percentage of maximal CVC, and were monitored using laser Doppler imaging. SNP Iontophoresis was performed on the ventral surface of the forearm, 1 h after application of lidocaine/prilocaine cream. Key results:  Sildenafil at 100 mg, but not 50 mg, increased overall responses (area under the curve) (44%) and peak responses (29%) to SNP Iontophoresis. Sildenafil at 100 mg, but not 50 mg, increased baseline CVC (75%). Incidence of headache was not changed when SNP Iontophoresis was combined with sildenafil. One episode of symptomatic arterial hypotension occurred in a volunteer given 50 mg sildenafil, 30 min after the beginning of SNP Iontophoresis. Conclusions and implications:  Oral sildenafil at 100 mg potentiated local skin hyperaemia induced by SNP Iontophoresis, with no increased incidence of headaches. The combination of oral specific PDE5A inhibitor and nitrates administered through skin Iontophoresis deserves further investigation in diseases such as severe Raynaud's phenomenon, with particular attention to the incidence of arterial hypotension.

RICHARD HENRY GUY - One of the best experts on this subject based on the ideXlab platform.

  • Iontophoretic transdermal sampling of iohexol as a non-invasive tool to assess glomerular filtration rate
    Pharmaceutical Research, 2015
    Co-Authors: Asma Djabri, William Van'T Hoff, Ian C K Wong, Penelope Brock, RICHARD HENRY GUY
    Abstract:

    Purpose To explore the potential of non-invasive reverse Iontophoresis transdermal extraction of iohexol as a marker of glomerular filtration rate. Methods A series of in vitro experiments were undertaken to establish the feasibility of iohexol reverse Iontophoresis and to determine the optimal conditions for the approach. Subsequently, a pilot study in paediatric patients was performed to provide proof-of-concept. Results The iontophoretic extraction fluxes of iohexol in vitro were proportional to the marker subdermal concentration and the reverse iontophoretic technique was able to track changes dynamically in simulated pharmacokinetic profiles. Reverse Iontophoresis sampling was well tolerated by the four paediatric participants. The deduced values of the iohexol terminal elimination rate constant from transdermal reverse Iontophoresis sampling agreed with those estimated by conventional blood sampling. Conclusions Reverse iontophoretic transdermal extraction fluxes mirrored the subdermal concentration profiles of iohexol, a relatively large neutral marker of glomerular filtration both in vitro and in vivo. The efficiency of extraction in vivo was well predicted by the in vitro model used.

  • Reverse Iontophoresis of amino acids: Identification and separation of stratum corneum and subdermal sources in vitro
    Pharmaceutical Research, 2009
    Co-Authors: C C Bouissou, Jean Philippe Sylvestre, RICHARD HENRY GUY
    Abstract:

    PURPOSE: To differentiate the stratum corneum (SC) and subdermal sources of amino acids (AAs) extracted by reverse Iontophoresis.\n\nMETHODS: 13 zwitterionic AAs were quantified in this in vitro study. Repetitive tape-stripping permitted the distribution of the analytes to be determined in the SC. Iontophoresis experiments were performed in which the subdermal chamber contained either phosphate-buffered saline (PBS) only, or a mixture of the 13 AAs in PBS.\n\nRESULTS: AAs were homogeneously distributed across the SC and broadly divided into three groups (high, medium, low) in terms of total amount present. As expected, extraction to the cathode for the essentially neutral analytes involved was more efficient. Initial samples obtained during the first hour of Iontophoresis primarily extracted AAs from the SC. The fluxes observed in the latter half of the 6-h experiment, on the other hand, correlated well with the corresponding subdermal concentrations.\n\nCONCLUSION: A relatively short extraction period (approximately 1 h) by reverse Iontophoresis can be used to evaluate the content of AAs in the SC. Once this 'reservoir' has been depleted, reverse Iontophoresis can then monitor the subdermal concentrations of the AAs. The latter appears most useful for compounds which are present at lower levels in the SC.

  • Non-invasive diagnosis and monitoring of chronic kidney disease by reverse Iontophoresis of urea in vivo
    European Journal of Pharmaceutics and Biopharmaceutics, 2008
    Co-Authors: Valentine Wascotte, Ana Salvaterra, Michel Jadoul, RICHARD HENRY GUY, Eric Rozet, Philippe Hubert, Véronique Préat
    Abstract:

    Background: Reverse Iontophoresis uses a small current to extract molecules and ions through the skin. The aim of the study was to determine whether reverse Iontophoresis of urea can be used (i) to diagnose and monitor non-invasively chronic kidney disease (CKD), and (ii) to track urea levels closely during a hemodialysis session. Methods: A current of 0.8 mA was applied for 2 h in 10 healthy volunteers, in 9 patients with CKD, and in 10 patients undergoing hemodialysis. Urea fluxes extracted by reverse Iontophoresis and urea concentrations in the blood were measured. Results: Extracted urea fluxes discriminated healthy volunteers from patients with CKD within 90 min. A non-invasive measure of blood urea concentrations can be achieved after 120 min. A urea reservoir in the skin interferes with the extraction and a pre-hemodialysis "depletion" period is required. Mild and transient sensation and erythema induced by Iontophoresis were significantly lower in the CKD group. Gelling the formulation of the Iontophoresis reservoir gave similar results to those obtained when using a simple aqueous solution. Conclusions: Reverse Iontophoresis can be used to non-invasively diagnose individuals with CKD and to monitor urea concentrations in blood. ?? 2008 Elsevier B.V. All rights reserved.

  • Reverse Iontophoresis of lithium: Electrode formulation using a thermoreversible polymer
    European Journal of Pharmaceutics and Biopharmaceutics, 2005
    Co-Authors: Valentine Wascotte, RICHARD HENRY GUY, Benoît Leboulanger, M. Begoña Delgado-Charro
    Abstract:

    This work investigated the use of a thermoreversible gel as a collector vehicle in reverse Iontophoresis applications. A 20% (w/w) aqueous gel of Pluronic F127 was a suitable receptor medium to be used at the cathodal chamber. In vitro Iontophoresis experiments investigated the simultaneous extraction of lithium (analyte of interest) and sodium (used as an internal standard) into either a control buffer or a gelled receptor. The gelification process at room temperature provided a suitable consistency and contact with the skin surface during the Iontophoresis experiments. Subsequent cooling of the gelled solution to 4??C allows an easy recovery of lithium and sodium for later quantification. Both the lithium extraction fluxes and the lithium to sodium ratio of extraction fluxes were linearly related to the subdermal lithium concentration. On the whole, the results show that thermoreversible polymer solutions offer a simple and convenient way to handle samples in reverse Iontophoresis studies. ?? 2004 Elsevier B.V. All rights reserved.

  • Reverse Iontophoresis as a noninvasive tool for lithium monitoring and pharmacokinetic profiling
    Pharmaceutical Research, 2004
    Co-Authors: Benoît Leboulanger, Marc Fathi, RICHARD HENRY GUY
    Abstract:

    PURPOSE: Transdermal Iontophoresis was investigated as a noninvasive tool for drug monitoring and pharmacokinetic profiling. Lithium, a frequently monitored drug, was used as a model. The objectives were a) to demonstrate the linear dependence of the iontophoretic extraction flux of lithium on the subdermal concentration of the drug, b) to evaluate the capacity of Iontophoresis to monitor sudden changes in the subdermal level, c) to investigate the utility of reverse Iontophoresis as a tool in pharmacokinetic studies, and d) to examine the validity of an internal standard calibration procedure to render the method completely noninvasive. METHODS: Transdermal, iontophoretic extraction was performed in vitro using dermatomed pig-ear skin. The subdermal solution consisted of a physiological buffer containing lithium chloride at concentrations in the therapeutic range and two putative internal standards, sodium and potassium, at fixed physiological levels. The subdermal concentration of lithium was changed either in a stepwise fashion or by simulating one of two pharmacokinetic profiles. RESULTS: Lithium was extracted via electromigration to the cathode. A excellent correlation between subdermal lithium concentration and iontophoretic extraction flux was observed. Iontophoresis tracked sudden concentration changes and followed kinetic profiles. In addition, the effective elimination rate constant could be directly, and noninvasively, estimated from the extraction flux data. CONCLUSIONS: Reverse Iontophoresis is a potentially useful and noninvasive tool for lithium monitoring.

Patricia Connolly - One of the best experts on this subject based on the ideXlab platform.

  • Simulataneous transdermal extraction of glucose and lactate from human subjects by reverse Iontophoresis
    International Journal of Nanomedicine, 2008
    Co-Authors: TAK-SHING CHING, Patricia Connolly
    Abstract:

    This study investigated the possibility of simultaneously extracting glucose and lactate from human subjects, at the same skin location, using transdermal reverse Iontophoresis. Transdermal monitoring using Iontophoresis is made possible by the skin's permeability to small molecules and the nanoporous and microporous nature of the structure of skin. The study was intended to provide information which could be used to develop a full, biosensor-based, monitoring system for multiple parameters from transdermal extraction. As a precursor to the human study, in vitro reverse Iontophoresis experiments were performed in an artificial skin system to establish the optimum current waveforms to be applied during Iontophoresis. In the human study, a bipolar DC current waveform (with reversal of the electrode current direction every 15 minutes) was applied to ten healthy volunteers via skin electrodes and utilized for simultaneous glucose and lactate transdermal extraction at an applied current density of 300 microA/cm2. Glucose and lactate were successfully extracted through each subject's skin into the conducting gel that formed part of each Iontophoresis electrode. The results suggest that it will be possible to noninvasively and simultaneously monitor glucose and lactate levels in patients using this approach and this could have future applications in diagnostic monitoring for a variety of medical conditions.

  • Reverse Iontophoresis: A non-invasive technique for measuring blood lactate level
    Sensors and Actuators B: Chemical, 2008
    Co-Authors: Congo Tak-shing Ching, Patricia Connolly
    Abstract:

    Blood lactate monitoring is beneficial to many patients, e.g. critical care patients. However, there are very few non-invasive or continuous monitoring systems for this parameter and significant clinical benefit could be achieved if such systems were readily available. Therefore, the aim of the current study was to investigate the possibility of non-invasively extracting lactate from blood through skin using reverse Iontophoresis to monitor blood lactate levels in humans. In vitro reverse Iontophoresis studies have indicated that the optimum switching mode for reverse Iontophoresis of lactate is continuous direct current but application of current combined with electrode polarity reversal every 15min was suggested to be used in humans. The reverse Iontophoresis technique was applied to 10 healthy volunteers and lactate was successfully extracted through their skin into the methylcellulose gel of the electrodes. A moderate correlation (r2=0.6) between lactate concentrations in collection gels and lactate levels in the blood was observed after an outlier was removed from the regression equation. The result suggests that it may be possible to non-invasively monitor the blood lactate levels using reverse Iontophoresis technique.

  • Reverse Iontophoresis: A New Approach to Measure Blood Glucose Level
    Asian Journal of Health and Information Sciences, 2007
    Co-Authors: Congo Tak-shing Ching, Patricia Connolly
    Abstract:

    This study focused on the investigation of the possibility of monitoring blood glucose levels in humans by non-invasively extracting glucose and lactate from blood through the skin using reverse Iontophoresis. In vitro reverse Iontophoresis studies have indicated that the optimum switching mode for reverse Iontophoresis of lactate and glucose are continuous direct current and direct current with electrode polarity reversal every 15 minutes, respectively. The application of a current combined with electrode polarity reversal every 15 minutes has been suggested for use in humans. The reverse Iontophoresis technique was applied to 10 healthy volunteers. Glucose and lactate were successfully extracted through the subjects' skin into the methylcellulose gel of the electrodes. A fair-good correlation (r 2 = 0.62) between the subject's blood glucose level and the ratio of glucose to lactate levels in the collection gels was observed after two outliers were removed from the regression equation. The result suggests that it may be possible to non-invasively monitor the blood glucose levels using this new approach free of the need for calibration with a blood sample.