Characterization of the permeability barrier of human skin in vivo

被引:153
|
作者
Pirot, F
Kalia, YN
Stinchcomb, AL
Keating, G
Bunge, A
Guy, RH
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT BIOPHARMACEUT SCI,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143
[3] LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94551
[4] COLORADO SCH MINES,DEPT CHEM ENGN,GOLDEN,CO 80401
[5] CTR INTERUNIV RECH & ENSEIGNEMENT,F-74166 ARCHAMPS,FRANCE
[6] UNIV GENEVA,FAC SCI,PHARM SECT,PHARM GALEN LAB,CH-1211 GENEVA,SWITZERLAND
关键词
D O I
10.1073/pnas.94.4.1562
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Attenuated-total-reflectance Fourier-transform-infrared spectroscopy has been used to rapidly and noninvasively quantify in vivo the uptake of a chemical into the outermost, and least permeable, layer of human skin (the stratum corneum), The objective of the experiment was to develop a general model to predict the rate and extent of chemical absorption for diverse exposure scenarios from simple, and safe, short-duration studies, Measurement of the concentration profile of the chemical in the stratum corneum, and analysis of the data using the unsteady-state diffusion equation, enabled estimation of the permeability coefficient and calculation of the time required to achieve maximal transdermal flux, Validation of the spectroscopic technique employed was established, and quantitation of chemical uptake into the stratum corneum was confirmed independently using trace amounts of radiolabeled chemical in conjunction with liquid scintillation counting and accelerator mass spectrometry. The results presented have pharmacological and toxicological implications, as the technology lends itself both to the prediction of transdermal drug delivery, and the feasibility of this route of administration, and to the assessment of risk after dermal contact with toxic chemicals.
引用
收藏
页码:1562 / 1567
页数:6
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