Noninvasive transdermal chemical collection. II. In vitro and in vivo skin permeability studies.
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.
Bradley
C R
CR
Uniformed Services University, Division of Clinical Pharmacology, Bethesda, Md.
Almirez
R G
RG
Conner
D P
DP
Rhyne
P R
PR
Peck
C C
CC
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
D005782:Gels; D002606:Charcoal; D010278:Parathion; D013806:Theophylline; D008727:Methotrexate