Transdermal Reverse Iontophoresis of Valproate: A Noninvasive Method for Therapeutic Drug Monitoring

Purpose. The objectives of this work were (a) to explore the potential of transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to develop an "internal standard” calibration procedure so as to render the technique completely noninvasive. Methods. A series of in vitro iontophoresis experiments was performed in which the subdermal concentration of sodium valproate was varied from 21 μM to 1 mM. Glutamic acid was also introduced into the subdermal donor at a fixed concentration to act as an "internal standard” for the calibration method. Results. Both valproate and glutamate anions were recovered, as expected, at the anodal receptor chamber. The iontophoretic extraction flux of valproate was linearly correlated with the subdermal concentration. Glutamate flux was constant. It follows that the ratio of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the subdermal valproate concentration and (b) the subdermal concentration ratio (valproate/glutamate), offering a means, thereby, to a completely noninvasive methodology. Conclusions. This work demonstrates the potential of reverse iontophoresis for noninvasive therapeutic monitoring. The simultaneous quantification of the analyte of interest and of an "internal standard” renders the withdrawal of a blood sample unnecessar

Reverse Iontophoresis as a Noninvasive Tool for Lithium Monitoring and Pharmacokinetic Profiling

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 monitorin

Perceptions about alcohol use during pregnancy in France, Portugal and Spain: a cross-cultural qualitative study

info:eu-repo/semantics/publishedVersio

Mathematical modelling of adjuvant-enhanced active ingredient leaf uptake of pesticides

The global importance of effective and affordable pesticides to optimise crop yield and to support health of our growing population cannot be understated. But to develop new products or refine existing ones in response to climate and environmental changes is both time-intensive and expensive which is why the agrochemical industry is increasingly interested in using mechanistic models as part of their formulation development toolbox. In this work, we develop such a model to describe uptake of pesticide spray droplets across the leaf surface. We simplify the leaf structure by identifying the outer cuticle as the main barrier to uptake; the result is a novel, hybrid model in which two well-mixed compartments are separated by a membrane in which we describe the spatio-temporal distribution of the pesticide. This leads to a boundary value partial differential equation problem coupled to a pair of ordinary differential equation systems which we solve numerically. We also simplify the pesticide formulation into two key components: the Active Ingredient which produces the desired effect of the pesticide and an Adjuvant which is present in the formulation to facilitate effective absorption of the Active Ingredient into the leaf. This approach gives rise to concentration-dependent diffusion. We take an intuitive approach to parameter estimation using a small experimental data set and subsequently demonstrate the importance of the concentration-dependent diffusion in replicating the data. Finally, we demonstrate the need for further work to identify how the physicochemical properties of pesticides affect flow into and across the leaf surface

Exploring the Consistency of Data Collected in Archaeological Geophysics: A Case Study from the Iron Age Hillfort of Villasviejas del Tamuja (Extremadura, Spain)

Different geophysical methods applied at the settlement of Villasviejas del Tamuja (Botija, Spain) have identified robust anomalies located at the same position, but some anomalies are reflected by only one method. Furthermore, analysing the spatial correlation of these anomalies is of fundamental importance for obtaining a correct archaeological interpretation. In this work, we analysed the main results of electrical resistivity tomography (ERT), ground-penetrating radar (GPR) and magnetic gradiometry methods in a particular area of the archaeological site. In this analysis, we performed graphical and numerical spatial correlation analyses of the anomalies and observed strong agreement among the results provided by each method. Certain anomalies were reflected only in the magnetic and ERT studies. The results highlight the importance of applying several geophysical methods and performing spatial correlational analyses. Furthermore, the methodology that we have applied to evaluate the spatial correlation offers interesting results

Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics

[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.This research was funded by Ministerio de Ciencia e Innovación (AP2007-03456) and the Universidad CEU Cardenal Herrera.Calatayud-Pascual, M.; Sebastian-Morelló, M.; Balaguer-Fernandez, C.; Delgado-Charro, M.; Lopez-Castellano, A.; Merino Sanjuán, V. (2018). Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics. Pharmaceutics. 10(4):1-15. https://doi.org/10.3390/pharmaceutics10040265S11510