PERCUTANEOUS-ABSORPTION OF ESTRADIOL AND PROGESTERONE IN NORMAL AND APPENDAGE-FREE SHIN OF THE HAIRLESS RAT - LACK OF IMPORTANCE OF NUTRITIONAL BLOOD-FLOW
F. Hueber et al., PERCUTANEOUS-ABSORPTION OF ESTRADIOL AND PROGESTERONE IN NORMAL AND APPENDAGE-FREE SHIN OF THE HAIRLESS RAT - LACK OF IMPORTANCE OF NUTRITIONAL BLOOD-FLOW, Skin pharmacology, 7(5), 1994, pp. 245-256
Percutaneous absorption occurs after passive diffusion through the dif
ferent layers of the skin and its appendages. Thereafter, a resorption
process into the cutaneous microcirculation brings the compounds into
the systemic circulation. The objective of this in vivo study in the
hairless rat was to compare the percutaneous absorption of two steroid
s on normal and appendage-free (scar) skin and to show if differences
in absorption result only from the lack of hair follicles and sebaceou
s glands and/or from a modification of local blood flow. Percutaneous
absorption was evaluated with estradiol and progesterone after 30 min,
2 and 6 h. Except after 30 min, the reservoir function of the stratum
corneum of scar skin was approximately twice as high as in normal ski
n. Eighty to ninety percent of the estradiol and progesterone found in
the stratum corneum were located in its superficial layers. Inversely
, whatever the application time was, the concentrations of both steroi
ds in the epidermis and dermis were significantly higher in normal ski
n than in scar skin with maximal difference between about 40 and 400 m
u m, the area of sebaceous gland localization. Cutaneous blood flow in
full-thickness skin, assessed by the thallium-201 method, was globall
y identical in normal and in scar skin. In scar skin, at the level of
papillary dermis, a decrease in blood flow due to the thicker viable e
pidermis and the flat dermoepidermal junction has been shown without i
mplying an accumulation of drug in the epidermis and superficial dermi
s. Under these conditions, our results clearly demonstrate that the nu
tritional blood flow does not interfere with the percutaneous absorpti
on of estradiol and progesterone in normal and scar skin. Thus, they c
onfirm the significant contribution of hair follicles and sebaceous gl
ands to drug penetration into the skin and subsequently the systemic c
irculation.