Noninvasive characterization of regional variation in drug transport into human stratum corneum in vivo.
OBJECTIVE
To investigate the mechanisms underlying the regional variations in drug transport into human stratum corneum (SC) of two model compounds of different lipophilicity and molecular size, 4-cyanophenol (CP) and cimetidine (CM), in vivo by non-invasive, quantitative attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy.


METHODS
Saturated solutions of CP and CM were applied to the skin surface of eleven Chinese men, at five anatomical sites, including forearm, back, thigh, leg, and abdomen, for 10-15 min and 3-5 h, respectively. After the skin surface was cleansed of remaining chemicals, the SC was tape-stripped sequentially up to 20 times, and the drug concentration profiles in the tape-stripped SC were determined using ATR-FTIR spectroscopy. Thickness of the SC was estimated simultaneously using two-point measurements of transepidermal water loss before and after completion of tape stripping. Estimation of partition, diffusion, and permeability coefficients was achieved by analysis of the data using the unsteady-state diffusion equation.


RESULTS
The rank orders of regional variation in partition and diffusion coefficients of CP and CM were different. The rank order of regional variation in permeability coefficients was similar for both drugs and decreased in the order of back > forearm > thigh > leg > or = abdomen, but the variation was more prominent for CM.


CONCLUSIONS
Regional variation in SC transport of CP was mainly influenced by its intrinsic diffusivity across the SC, whereas variation in transport of CM could be attributed to both thermodynamic and kinetic differences among different anatomical skin sites.
Tsai
Jui-Chen
JC
Institute of Clinical Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. jctsai@mail.ncku.edu.tw
Lin
Ching-Yu
CY
Sheu
Hamm-Ming
HM
Lo
Yu-Li
YL
Huang
Ying-Hsuan
YH
D000279:Administration, Cutaneous; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D002681:China; D002927:Cimetidine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008954:Models, Biological; D010539:Permeability / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared; D014870:Water Loss, Insensible / Q000187:drug effects / Q000502:physiology
D010636:Phenols; C007178:4-cyanophenol; D002927:Cimetidine