Convective solvent flow across the skin during iontophoresis.
Enhanced flux of neutral solutes during transdermal iontophoresis is attributed largely to electroosmotic volume flow. In this study, the iontophoretic fluxes of tritiated water (3H2O) and 14C-labeled mannitol through hairless mouse skin (HMS) were determined. The following questions were addressed: (i) What is the variability of water flux during iontophoresis? (ii) To what extent is the iontophoretic flux of a neutral solute correlated with water flux? (iii) Does the intrinsic permeability of the skin to neutral solutes change following iontophoresis? (iv) What is the effect of low pH on electroosmotic volume flow? and (v) Does the skin remain permselective after removal of the stratum corneum? Transport of both water and mannitol reached steady-state levels during 10 hr of constant-current iontophoresis (0.36 mA/cm2). Anodal fluxes exceeded cathodal values. Cathodal mannitol flux was retarded, relative to passive transport, by net volume flow in the opposite direction, such that transport of this molecule increased significantly after the termination of current passage. Anodal equivalent volume flows for water and mannitol, respectively, were 2.7 (+/- 1.3) and 1.23 (+/- 0.59) microL/hr cm2, indicating that only approximately 50% of the water flux participated in the electroosmosis of mannitol. The passive permeability of water and mannitol after 10 hr of iontophoresis was, respectively, 6 and 30 times greater than the pretreatment values. At pH 7, the cationic permselectivity of HMS was marginal [the Na+ transport number (tNa+) was determined to be 0.46] and less than that reported for human skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Kim
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Department of Pharmacy, University of California, San Francisco 94143.
Green
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Rao
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Guy
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D000279:Administration, Cutaneous; D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis; D008353:Mannitol / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008812:Mice, Hairless; D009994:Osmolar Concentration; D012869:Skin Absorption / Q000502:physiology*; D012964:Sodium / Q000493:pharmacokinetics; D012997:Solvents
D002712:Chlorides; D012997:Solvents; D008353:Mannitol; D012964:Sodium