Transcutaneous collection of theophylline: constancy and linearity of skin permeability.
Transcutaneous chemical collection is a novel method for noninvasive collection and measurement of body exposure to chemicals using a transcutaneous collection device (TCD) consisting of a circular adhesive-tape-encased saline-activated carbon-aquagel patch. The objectives of this study were to determine (1) the time-course of skin permeability change after the placement of a TCD on the skin, and (2) the relationship between the amount of theophylline collected in a TCD and the amount of theophylline in the body as expressed by the area under the plasma concentration-time curve (AUC). Skin permeability changes were determined by emplacing TCDs (24/monkey) on the chests and abdomens of female rhesus monkeys (12 studies in 4 monkeys) at 48, 24, 6, 3 and 1 h prior to dosing with aminophylline (10 mg/kg of theophylline, i.v.) over 30 min. Several blood samples were collected, and TCDs were removed at 24 h post-dose; samples were assayed for theophylline by HPLC. The apparent permeability coefficients (Kp) increased following TCD placement reaching 90% of maximum by 17 h. The relationship between the amount of theophylline collected in the device (Q) and amount in the body over time was determined by emplacing TCDs on rhesus monkeys (8 studies in 4 monkeys) 24 h prior to administration of 10 mg/kg of theophylline. Qs from the TCDs removed at 0.17, 0.5, 1, 3, 6 and 24 h were linearly related to the plasma AUC according to the relationship: Q = (A x Kp) x AUC, where A is the area of gel in contact with the skin for each TCD.
Conner
D P
DP
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Md.
Almirez
R G
RG
Rhyne
P
P
Zamani
K
K
Bolden
B J
BJ
Peck
C C
CC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008253:Macaca mulatta; D008297:Male; D010539:Permeability; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013048:Specimen Handling; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
D013806:Theophylline