Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats.
The effect of age on intact and stripped skin permeability of lipophilic (ketoprofen and isosorbide dinitrate) and hydrophilic permeants (deuterium oxide and diclofenac sodium) was investigated using STD: Wistar male rats aged 5 to 180 days. The permeability of permeants through intact skin increased with increasing lipophilicity of the permeants at each age, indicating that the permselective property of rat skin is revealed even at 5-days-old. The permeability coefficients through intact skin decreased with increasing age, and the extent of these decreases was higher for lipophilic permeants than that for hydrophilic permeants. On the other hand, the stripped skin permeability of permeants was almost the same at each age, and with aging each permeability coefficient through stripped skin decreased up to 21 days, dramatically during 21-90 days and then gradually again to 180 days. The thickness of the stratum corneum and stripped skin increased according to age with faster growth during 21-90 days. The reciprocal of the mean thickness of stratum corneum and stripped skin correlated well with intact skin and stripped skin permeability (r > 0.9), respectively. These results clarified that the permselectivity of rat skin against lipophilicity of permeant exists at the latest from 5 days after birth. In addition, it is speculated that the thickness of skin is a large factor in the decrease of its permeability with age.
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan.
T
T
Ngawhirunpat
H
H
Yoshikawa
T
T
Hatanaka
T
T
Koizumi
I
I
Adachi
D000375:Aging; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D017666:Deuterium Oxide / Q000737:chemistry / Q000493:pharmacokinetics; D004008:Diclofenac / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000033:anatomy & histology / Q000737:chemistry / Q000254:growth & development*; D012869:Skin Absorption / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D004008:Diclofenac; D007660:Ketoprofen; D017666:Deuterium Oxide