Visualization of percutaneous 3H-estradiol and 3H-norethindrone acetate transport across human epidermis as a function of time.
Developing transdermal therapeutic systems for estradiol and norethindrone acetate raised questions about the steroids penetration pathway across and retention in the skin. This paper describes the distribution of 3H-estradiol and 3H-norethindrone acetate in human stratum corneum after topical application to dermatomed skin in vitro. The study involved (a) permeation experiments to determine the steroid flux, (b) autoradiographical visualization of the steroid distribution in the same skin samples, and (c) a correlation between flux and skin distribution in time. On correlating the steroid flux with intraepidermal steroid distribution, it was concluded that both permeants were bound in the skin tissue. The steroids were preferentially located in or close to the intercellular lipids of the stratum corneum, indicating that both transport and binding occurred via this domain of the stratum corneum. This study demonstrated the importance of correlating drug flux with intraepidermal drug distribution as a function of time.
Neelissen
J A
JA
AstraZeneca R&D Södertälje, Biopharmaceutics, Sweden. jan.neelissen@astrazeneca.com
Arth
C
C
Wolff
M
M
Schrijvers
A H
AH
Junginger
H E
HE
Boddé
H E
HE
D000279:Administration, Cutaneous; D001345:Autoradiography; D001692:Biological Transport; D004817:Epidermis / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000077563:Norethindrone Acetate; D010539:Permeability; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D012869:Skin Absorption / Q000187:drug effects; D013997:Time Factors; D014316:Tritium
D045167:Progesterone Congeners; D019275:Radiopharmaceuticals; D014316:Tritium; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone