title: Noninvasive transdermal chemical collection. II. In vitro and in vivo skin permeability studies.
abstract: In vitro and in vivo skin permeability studies were conducted to investigate properties of several candidate transdermal chemical collection devices (TCDs). The TCD consists of a binding reservoir of activated charcoal suspended in a gel medium which is occlusively placed in direct contact with the skin. Binding of three model compounds (theophylline, methotrexate, and parathion) was studied in hydrophilic (agarose or PVA/PVP) and lipophilic (silicone) gel/carbon compositions. The effects of gel composition, compound hydrophilicity/lipophilicity, and hydration of skin on quantity of transdermally collected chemical and 'apparent' permeability were investigated using a 'fuzzy' rat animal model. In vitro and in vivo apparent permeability coefficients (Kp; cm/h) for amphophilic theophylline (6.95 x 10(-4) and 8.34 x 10(-4), respectively) and hydrophilic methotrexate (3.5 x 10(-3) and 3.2 x 10(-4), respectively) using an agarose aquagel TCD were greater than the corresponding Kp values obtained when silicone lipogel TCDs were employed (0.3 x 10(-4) and 3.2 x 10(-4), respectively, for theophylline; no measurable methotrexate was collected). Occlusive hydration of skin profoundly increased permeability of the hydrophyilic model compound, methotrexate. In vivo Kp values for lipophilic parathion were greater with a silicone TCD (6.7 x 10(-4) than with an agarose TCD (3.8 x 10(-4). We conclude that it is possible to influence transdermal chemical collection through modifications in the gel composition and by hydration of the skin.
authors.affiliation: Uniformed Services University, Division of Clinical Pharmacology, Bethesda, Md.
authors.forename: C R
authors.initials: CR
authors.lastname: Bradley
authors.forename: R G
authors.initials: RG
authors.lastname: Almirez
authors.forename: D P
authors.initials: DP
authors.lastname: Conner
authors.forename: P R
authors.initials: PR
authors.lastname: Rhyne
authors.forename: C C
authors.initials: CC
authors.lastname: Peck
mesh_terms: D000818:Animals; D002606:Charcoal / Q000378:metabolism; D005782:Gels; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics; D010278:Parathion / Q000493:pharmacokinetics; D010539:Permeability; D010600:Pharmacology / Q000379:methods*; D051381:Rats; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013806:Theophylline / Q000493:pharmacokinetics
chemical_list: D005782:Gels; D002606:Charcoal; D010278:Parathion; D013806:Theophylline; D008727:Methotrexate