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Lithium Monitoring by Reverse Iontophoresis in Vivo

¹ School of Pharmacy and ² Department of Psychiatry, University of Geneva, Geneva, Switzerland.
³ Centre International de Recherche et d’Enseignement ("Pharmapeptides"), Archamps, France.

^aAddress correspondence to this author at: School of Pharmacy, University of Geneva, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland. Fax 33-4-50-95-28-32; e-mail begonia.delgado{at}pharm.unige.ch.

Background: We investigated reverse transdermal iontophoresis as an alternative, noninvasive method for lithium monitoring in vivo. The objectives of such an approach would be to facilitate compliance with treatment and to improve the quality of life for bipolar patients.

Methods: We studied 23 bipolar or schizo-affective patients. Over a 2-h period, we extracted lithium and other cations across intact skin by application of an electric current (0.8 mA) and quantified the concentrations by ion chromatography. A blood sample provided comparative reference values for the drug and other electrolytes.

Results: Lithium, sodium, potassium, and calcium were efficiently extracted by iontophoresis. Lithium extraction fluxes were proportional to the corresponding serum concentrations, whereas sodium, potassium, and calcium extraction fluxes were relatively constant, consistent with their stable concentrations in blood. Normalization of the lithium extraction flux with that of sodium, which acted as an "internal standard", permitted calibration of the monitoring procedure without the need for a blood measurement. This conclusion was tested retrospectively by dividing the patients into two groups. The reverse iontophoretic extraction data from the first subset (a) established the proportionality between lithium iontophoresis (or the relative electrotransport of lithium and sodium) and (b) predicted lithium blood concentrations in the second subset of patients. The predictive ability was very good, with the internal standard concept providing substantial benefit.

Conclusions: Reverse iontophoresis appears to offer a novel and accurate method for lithium monitoring.

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