RESUMEN
A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was -0.01 and 0.26 mmol l(-1) for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l(-1) for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l(-1) h(-1), which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.
Asunto(s)
Automonitorización de la Glucosa Sanguínea/instrumentación , Diabetes Mellitus/sangre , Automonitorización de la Glucosa Sanguínea/estadística & datos numéricos , Diabetes Mellitus/metabolismo , Diseño de Equipo , Glucosa/metabolismo , Humanos , Iontoforesis , Piel/metabolismoRESUMEN
OBJECTIVE: Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose < or = 3.9 mmol/l. RESEARCH DESIGN AND METHODS: The analysis was based on 1,091 biographer uses from four clinical trials. which generated 14,487 paired (biographer and blood glucose) readings. RESULTS: The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose < or = 3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose >3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer.
Asunto(s)
Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Hipoglucemia/diagnóstico , Monitoreo Ambulatorio/instrumentación , Automatización , Automonitorización de la Glucosa Sanguínea/métodos , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Hipoglucemia/sangre , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Monitoreo Ambulatorio/métodos , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Improved glycemic control significantly reduces long-term microvascular complications of diabetes mellitus associated with chronic hyperglycemia. The GlucoWatch biographer is designed to facilitate intensive diabetes management by providing automatic, frequent, and noninvasive glucose readings up to three times per hour for as long as 12 hours. METHODS: The device extracts glucose through intact skin using reverse iontophoresis and measures the extracted glucose with an electrochemical biosensor. A clinical trial was performed to assess the effect of acetaminophen, a potential interference for traditional blood glucose meters, on the accuracy of the GlucoWatch biographer in adult subjects with diabetes (n = 18). One thousand milligram doses of acetaminophen were administered to subjects in two groups: one to achieve Cmax (peak acetominophen concentration) at the time of biographer calibration and the other to achieve Cmax during the measurement period. The biographer readings were compared to serial fingerstick blood glucose measurements. RESULTS: Time profiles over 9 hours show close tracking of the biographer glucose results with fingerstick blood glucose measurements for all groups. The mean difference between the two measurements is between 8 and 12 mg/dL for all groups. The mean absolute value of the relative difference is less than 20%, and more than 93% of the points were in the clinically acceptable (A+B) region of the Clarke Error Grid. No statistically significant differences were found for any accuracy measurement across all groups. CONCLUSIONS: The GlucoWatch Biographer provides frequent measurements of glucose over a 12-hour period with high accuracy. No effect of therapeutic dosage of acetaminophen on the accuracy of the glucose readings was found.
Asunto(s)
Acetaminofén/farmacología , Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/métodos , Adulto , Análisis de Varianza , Automatización , Técnicas Biosensibles , Automonitorización de la Glucosa Sanguínea/instrumentación , Calibración , Electroquímica , Diseño de Equipo , Humanos , Reproducibilidad de los Resultados , Factores de Tiempo , Estados Unidos , Población BlancaRESUMEN
The GlucoWatch (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients.
Asunto(s)
Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus/sangre , Análisis de Varianza , Técnicas Biosensibles , Automonitorización de la Glucosa Sanguínea/instrumentación , Ensayos Clínicos como Asunto , Diseño de Equipo , Femenino , Humanos , Hipoglucemia/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
CONTEXT: Intensive diabetes management using frequent blood glucose measurements to guide therapy has been shown to significantly improve short- and long-term outcomes. Development of a device that makes possible frequent, automatic, painless, and accurate measurements of glucose would facilitate intensive management. OBJECTIVE: To determine the accuracy of the GlucoWatch automatic glucose biographer (Cygnus Inc) compared with that of serial blood glucose measurements. DESIGN: Multicenter comparative study of the GlucoWatch biographer and the HemoCue blood glucose analyzer (Aktiebolaget Leo) performed between August 29 and October 17, 1998. Participants wore up to 2 biographers during the 15-hour study session and performed 2 fingersticks per hour for comparative blood glucose measurements. The biographers were calibrated with a single HemoCue measurement after a 3-hour warm-up period. Diet and insulin were manipulated to produce a broad glycemic range during the study. SETTING: Controlled clinical environment at 2 diabetes centers and 3 contract research organizations in the United States. PARTICIPANTS: A total of 92 subjects (mean [SD] age, 42.1 [15.1] years; 59.8% women) with type 1 or 2 diabetes requiring treatment with insulin. MAIN OUTCOME MEASURES: Mean error, mean absolute error, correlation, slope, and intercept using Deming regression, and clinical significance of differences between biographer readings and blood glucose measurements using the Clarke error grid. RESULTS: Results showed close tracking of blood glucose over a range of 2.2 to 22.2 mmol/L (40-400 mg/dL) for up to 12 hours using a single point calibration. The biographer readings lagged behind serial blood glucose values by a mean of 18 minutes. An analysis of 2167 data pairs shows a linear relationship (r = 0.88; slope = 1.03; intercept = -0.33 mmol/L [-6 mg/dL]) between biographer readings and serial glucose measurements. The mean absolute error between the 2 measurements was 15.6% (mean error [SD], -0.07 [1.82] mmol/L [-1 [33] mg/dL]), and 96.8% of the data fell in the therapeutically relevant regions of the error grid analysis. CONCLUSION: These results demonstrate close agreement between GlucoWatch biographer readings and blood glucose measurements using repeated fingerstick blood samples. The automatic, frequent, and noninvasive measurements obtained with the biographer provides more information about glucose levels than the current standard of care.
Asunto(s)
Técnicas Biosensibles , Automonitorización de la Glucosa Sanguínea/instrumentación , Adulto , Glucemia/análisis , Diabetes Mellitus/prevención & control , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: The purpose of this study was to compare measurements of glucose obtained via iontophoretic extraction with the GlucoWatch automatic glucose biographer (Cygnus, Inc., Redwood City, CA) with capillary blood glucose values that were determined 1) in a controlled outpatient clinic setting and 2) in a home setting. RESEARCH DESIGN AND METHODS: There were 76 GlucoWatch biographers used on 28 different young adults (21 women and 7 men) with type 1 diabetes (age 30.9 +/- 6.9 years and duration of diabetes 18.4 +/- 8.1 years [mean +/- SD]) in a controlled outpatient clinic setting. Some subjects participated on multiple days. Subjects wore two GlucoWatch biographers, each on the forearm (ventral aspect). Comparisons were made to HemoCue blood glucose analyzer (Aktiebolgat Leo, Helsingborg, Sweden) capillary blood glucose measurements. In addition, GlucoWatch biographers (one each day for 3 consecutive days) were used by 12 subjects (8 women, 4 men) in a home setting. Comparisons were made to capillary blood glucose values determined using the One Touch Profile meter (Johnson & Johnson, New Brunswick, NJ). RESULTS: GlucoWatch biographer glucose values correlated well with capillary blood glucose values determined using the HemoCue analyzer in the clinic setting (r = 0.90, 1,554 paired data points) and using the One Touch Profile meter in the home setting (r = 0.85, 204 paired data points). When 36 subjects wore two biographers simultaneously, the correlation between the two biographers was r = 0.94. The error grid analysis demonstrated that > 96% of biographer glucose values determined in the clinic or home setting were in the clinically acceptable A and B regions. CONCLUSIONS: This study confirms the accuracy and precision of glucose values as determined using the GlucoWatch biographer in clinic and home settings.
Asunto(s)
Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 1/sangre , Adulto , Capilares , Diseño de Equipo , Femenino , Dedos/irrigación sanguínea , Humanos , Masculino , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
Using fluorescence techniques, we studied the dynamics of the lipid bilayer matrix of human stratum corneum (SC) and compared the results with that of distearoyl-phosphatidylcholine (DSPC). We employed a series of 9-anthroyloxy fatty acids (AF) that partitioned into the bilayer, enabling us to evaluate this structure as a function of depth within the lamellae. With AF probes, the re-orientation of the fluorophore is known to be affected by the polarity, hydrogen bonding, and rigidity of the surrounding medium, altering the emission maximum and lifetime in the excited state. In addition, we evaluated quenching, in which iodide collides with the fluorophore, revealing information on the accessibility of the fluorophore located in the bilayer. The emission and lifetime data showed that the reorientation of the fluorophore in SC was more hindered than in DSPC, indicating that SC bilayers were more rigid than DSPC bilayers. Quenching data of both SC and DSPC indicated that the deeper the fluorophore was positioned in the bilayer, the less accessible it was to iodide, pointing to a gradient in accessibility. In addition, the quenching results also showed that the SC is less accessible to iodide than in DSPC. The observed differences in bilayer rigidity and quencher accessibility between the two systems can be explained by differences in lipid composition and hydration. Whereas the DSPC bilayer consists of phospholipids, SC bilayers are composed of more anhydrous lipids like cholesterol and ceramides, which form a tight bilayer packing. In this way SC lipids exist in a relatively anhydrous and rigid environment, forming an effective diffusion barrier to water and ions.
Asunto(s)
Epidermis/metabolismo , Metabolismo de los Lípidos , Ácidos Grasos/química , Colorantes Fluorescentes , Humanos , Yoduros/farmacología , Membrana Dobles de Lípidos/química , Modelos Biológicos , Fosfatidilcolinas/metabolismo , Espectrometría de FluorescenciaRESUMEN
The electrical properties of the outermost layer of skin are described by lipid-corneocyte (Zm) and appendageal (Za) impedance, which are connected in parallel. Appendageal macropores are considered as long tubes with distributed electrical parameters. It has been shown that not only Za, but also the macropore resistance Ra and capacitance Ca are frequency dependent. The input of Za in the overall impedance (Z) depends on the space density of active (conductive) macropores n(i), which increase with current density (i) and the duration of iontophoresis. Skin impedance has been demonstrated to decrease under the influence of iontophoretic treatment. Application of the theoretical model to these data provides an estimate of the increase in macropore density during iontophoresis. A comparison of these results with n(i), which was measured directly, shows a strong correlation supporting this unique model.
Asunto(s)
Folículo Piloso/fisiología , Modelos Biológicos , Fenómenos Fisiológicos de la Piel , Glándulas Sudoríparas/fisiología , Animales , Conductividad Eléctrica , Impedancia Eléctrica , Ferrocianuros/farmacocinética , Iontoforesis , Metabolismo de los Lípidos , Ratones , Ratones Pelados , Piel/citología , Piel/metabolismoRESUMEN
The electrical properties of human skin in the range of the applied voltages between 0.2 and 60 V are modeled theoretically and measured experimentally. Two parallel electric current pathways are considered: one crossing lipid-corneocyte matrix and the other going through skin appendages. The appendageal ducts are modeled as long tubes with distributed electrical parameters. For both transport systems, equations taking into account the electroporation of lipid lamella in the case the lipid-corneocyte matrix or the walls of the appendageal ducts in the case of the skin appendages are derived. Numerical solutions of these nonlinear equations are compared with published data and the results of our own experiments. The current-time response of the skin during the application of rectangular pulses of different voltage amplitudes show a profound similarity with the same characteristics in model and plasma membrane electroporation. A comparison of the theory and the experiment shows that a significant (up to three orders of magnitude) drop of skin resistance due to electrotreatment can be explained by electroporation of different substructures of stratum corneum. At relatively low voltages (U < 30 V) this drop of skin resistance can be attributed to electroporation of the appendageal ducts. At higher voltages (U > 30 V), electroporation of the lipid-corneocyte matrix leads to an additional drop of skin resistance. These theoretical findings are in a good agreement with the experimental results and literature data.
Asunto(s)
Fenómenos Fisiológicos de la Piel , Estimulación Eléctrica , Electrofisiología/métodos , Femenino , Humanos , Técnicas In Vitro , Membrana Dobles de Lípidos , Masculino , Matemática , Modelos Biológicos , Piel/anatomía & histología , Piel/citologíaRESUMEN
The aim of this study was to develop methods to determine ionic transport parameters, in particular ionic mobilities across human stratum corneum (SC) in vivo. It has been shown previously that the SC, a structurally heterogeneous biomembrane, behaves as a homogeneous barrier to water transport; that is, water diffusivity does not vary as a function of position within the SC; in this work, therefore, the question posed was whether ion motion behaved similarly. Low-frequency impedance measurements (1.61 Hz) reported on the decrease of SC impedance as the barrier was progressively removed by serial adhesive tape stripping. This corresponded to an increase in ion mobility of approximately 2 orders of magnitude across the SC (from the external surface to the interior). Therefore, an algorithm was developed from the absolute impedance data to calculate ion mobility as a function of position within (i.e., depth into) the SC. The mobilities deduced from the algorithm correlated well with water permeability across the SC. The data presented here are thought to be the first measurements of ionic mobility across human skin in vivo.
Asunto(s)
Epidermis/metabolismo , Iones , Farmacocinética , Agua/metabolismo , Adulto , Impedancia Eléctrica , Femenino , Humanos , Masculino , PermeabilidadAsunto(s)
Administración Cutánea , Electroporación , Péptidos/administración & dosificación , Animales , Transporte Biológico , Calcitonina/administración & dosificación , Electroporación/efectos adversos , Hormona Liberadora de Gonadotropina/administración & dosificación , Insulina/administración & dosificación , Membrana Dobles de Lípidos/química , Neurotensina/administración & dosificación , Piel/metabolismo , Porcinos , Vasopresinas/administración & dosificaciónRESUMEN
A physical mechanism of activation of skin appendage macropores under the influence of an electric field is considered theoretically. The macropore is considered as a long cylinder tube which is closed and flattened out before the electric field is applied. The charging of the capacitance of the macropore walls is the driving force of electroactivation. During this process the free energy of the system decreases, which is energetically favourable and results in water pulled into the tube and to a gradual opening of the tube. It is shown that consideration of the macropore wall conductance leads to a considerable slowdown of electroactivation. The opening time of a separate macropore is estimated. It is equal to 30 min for a macropore 4 mm in length. The dependence of the surface density of activated macropores on time is calculated theoretically. The obtained theoretical results are in a good agreement with the literature data.
Asunto(s)
Iontoforesis/métodos , Piel/efectos de los fármacos , Glándulas Sudoríparas/química , Administración Cutánea , Sistemas de Liberación de Medicamentos , Respuesta Galvánica de la Piel/efectos de los fármacos , Humanos , Modelos Teóricos , Potenciometría , Fenómenos Fisiológicos de la Piel , Glándulas Sudoríparas/efectos de los fármacos , Factores de TiempoRESUMEN
PURPOSE: To study ion transport through stratum corneum (SC) lipid lamellae under passive and iontophoretic conditions. METHODS: Iodide ion transport was measured by fluorescence quenching. Since the process involves diffusion of an iodide ion to the fluorophore located within the SC lamellae, the accessibility of iodide ions was measured. Moreover, the use of anthroyloxy fatty acid probes, provided information as a function of depth within the lamellae. RESULTS: Fluorescence quenching by iodide ions increased with iontophoretic current density, suggesting increased ion accessibility within the SC lamellae. In addition, at constant current, quenching decreased as the fluorophore was located deeper within the lamellae. This gradient in ion accessibility suggests that more iodide is found near the head-group than near the core of the SC lipid lamellae. Results obtained in the absence of iodide also show increased water accessibility during iontophoresis. CONCLUSIONS: These results show that in the presence of an applied electric field the SC lipid lamellae interior becomes more accessible to water and ions. These results imply that during iontophoresis, ion and water transport through human skin is associated, at least in part, with the SC lipid lamellae.
Asunto(s)
Electricidad , Piel/metabolismo , Fluorescencia , Transporte Iónico , Iontoforesis , Fenómenos Fisiológicos de la PielRESUMEN
PURPOSE: To demonstrate that "reverse iontophoresis" can be used to noninvasively obtain information about systemic glucose levels in vivo in humans. METHODS: The passage of current across the skin in vivo drives ions into the tissue, from the electrode chambers positioned on the skin surface, and simultaneously pulls ions from the body in the opposite direction. Because of the net negative charge on the skin, under normal conditions, the membrane is permselective to cations, and a potential gradient also results, therefore, in electroosmotic convection of solvent in the direction of counterion flow (i.e., from anode to cathode). Thus, it is also possible to enhance the transport of polar, yet uncharged, species using iontophoresis. In an earlier study, the in vitro extraction of glucose, by "reverse iontophoresis" was established, and extension of the approach to an in vivo model was indicated. The idea has therefore been further explored in vivo in humans. RESULTS: Using small, simple, prototypical electrode chambers, attached to the ventral forearm surface, direct current iontophoresis at 0.25 mA/cm2 for periods of up to 1 hour, and a sensitive analytical procedure to measure the quantities of glucose extracted, it has been shown that iontophoretic sampling of glucose is feasible. However, the shorter periods (15 minutes or less) of extraction considered yield results which are "contaminated" (it is believed) by glucose that is a product of lipid metabolism within the skin. While this material is expected to complicate the initial calibration of the approach, the problem is effectively resolved within one hour, by which time the glucose arriving in the electrode chambers on the skin surface is expected to directly reflect the subcutaneous tissue concentration. CONCLUSIONS: Based upon these initial observations, further investigation can now be directed towards optimization of electroosmotic flow and sampling time, improved reproducibility and the development of a practical assay methodology.
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Glucemia/metabolismo , Glucosa/metabolismo , Iontoforesis/métodos , Humanos , CinéticaRESUMEN
Results from the Diabetes Care and Complications Trial show that tight blood glucose control significantly reduces the long-term complications of diabetes mellitus. In that study, frequent self-testing of glucose and insulin administration resulted in a significant reduction in long-term complications. This protocol, however, also resulted in a threefold increase in the frequency of hypoglycaemic incidents. Currently, self-testing requires a drop of blood for each measurement. The pain and inconvenience of self-testing, along with the fear and danger of hypoglycaemia has led to poor patient acceptance of a tight control regimen, despite the clear long-term advantages. A continuously worn, noninvasive method to periodically measure glucose would provide a convenient and comfortable means of frequent self-testing. A continuously worn device could also alert the user of low glucose levels, thereby reducing the incidence of hypoglycaemia. Guy et al. demonstrated a noninvasive method to transport glucose through the skin using low-level electrical current. To provide a quantitative measurement, the flux of glucose extracted across the skin must correlate with serum glucose in a predictive manner. The results presented here show a quantitative relationship between serum and transdermally extracted glucose in diabetics.
Asunto(s)
Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Diabetes Mellitus/sangre , Iontoforesis/métodos , Adulto , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Piel/metabolismoRESUMEN
PURPOSE: To develop a predictive algorithm of nonelectrolyte transport through skin based upon a partitioning-diffusion model. METHODS: Drug permeability is described by a partitioning-diffusion equation. Through free-energy relationships, partitioning is related to the drug's molecular volume (MV), and hydrogen bond donor (Hd) and acceptor (Ha) activity. Diffusion is related to the drug's MV using a theory of diffusion through lipid lamellae based on free-volume fluctuations within the lipid domain. These two explicit descriptions are combined to give an equation describing permeability in terms of the permeant's physical properties. The aqueous permeability coefficients of 37 nonelectrolytes through human epidermis were evaluated as a function of these physical properties using a multiple regression analysis. RESULT: The results of the regression analysis show that 94% of the variability in the data can be explained by a model which includes only the permeant's MV, Hd and Ha. These results further provide an algorithm to predict skin permeability based upon the values of these parameters. In addition, the relative contribution of various chemical functional groups (e.g., -COOH) is derived, and can be used to predict skin transport from drug structure alone. CONCLUSIONS: A biophysically relevant model of drug transport through human skin is derived based solely on the physical properties of the drug. The model provides an algorithm to predict permeability from the drug's structure and/or physical properties. Moreover, the model is applicable to a number of lipid barrier membranes, suggesting a common transport mechanism in all.
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Algoritmos , Epidermis/metabolismo , Absorción Cutánea/fisiología , Fenómenos Químicos , Química Física , Difusión , Humanos , Enlace de Hidrógeno , Cinética , Lípidos/química , Membranas Artificiales , Modelos Biológicos , Peso Molecular , Permeabilidad , Análisis de Regresión , SolubilidadRESUMEN
A theoretical model for electroporation of multilamellar lipid system due to a series of large electrical pulses is presented and then used to predict the functional dependence of the transport of charged molecules. Previously, electroporation has been considered only for single bilayer systems such as artificial planar bilayer membranes and cell membranes. The former have been extensively studied with respect to electrical and mechanical behavior, and the latter with respect to molecular transport. Recent experimental results for both molecular transport and electrical resistance changes in the stratum corneum (SC) suggest that electroporation also occurs in the multilamellar lipid membranes of the SC. In addition, there is the possibility that other skin structures (the "appendages") also experience electroporation. A compartment model is introduced to describe the transport of charged species across the SC, and the predicted dependence is compared with available data. In this model, the SC is assumed to contain many hydrophilic compartments in series separated by boundary bilayers, so that these compartments become connected only upon electroporation. Two limiting cases for the transport of charged molecules are considered: (1) transport along tortuous inter-bilayer pathways in each compartment, followed by transport across individual boundary bilayers due to electroporation, and (2) transport along straight-through pathways in the boundary bilayers with fast mixing in each compartment, which includes the interior space of corneocytes. Both models were fitted to the experimental data. The large electropore radius (rt approximately 200 A) and porated fractional area (ft approximately 10(-3) obtained from the fitting for the tortuous model relative to the more reasonable values obtained for the straight-through model (rs approximately 4 A, fs approximately 10(-6) suggest that the latter is a more realistic description of electroinduced transport of ionized species through the skin.