Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus.
For treatment of skin diseases with topical drugs, penetration of the agents into the relevant layers of the skin is required. Permeation through the skin should, however, be kept to a minimum, in order to avoid the risk of systemic side effects. Here we compared the in vitro skin penetration and permeation of two novel drugs used in the therapy of atopic eczema (pimecrolimus and tacrolimus) and three representative corticosteroids (betamethasone-17-valerate, clobetasol-17-propionate, and diflucortolon-21-valerate). Drug concentrations of pimecrolimus and corticosteroids in human skin were found to be in the same order of magnitude. Permeation of pimecrolimus through human skin was, however, lower by factors of 70-110 as compared to the steroids. When pimecrolimus was compared with tacrolimus in human, pig, or rat skin, similar concentrations of the two compounds were measured in the skin, whereas permeation of pimecrolimus through skin was consistently lower by factors of 9-10. Lipophilicity was found to be highest for pimecrolimus, its octanol-water distribution coefficient being higher by factors of 8 and 25-450 than that of tacrolimus and the corticosteroids, respectively. The low permeation of pimecrolimus may be explained by its higher lipophilicity (compared to tacrolimus and the corticosteroids) and higher molecular weight (compared to steroids). In conclusion, pimecrolimus appears to have a favourable skin penetration/permeation profile, featuring a low degree of percutaneous absorption.
Billich
Andreas
A
Novartis Research Institute Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria. andreas.billich@pharma.novartis.com
Aschauer
Heinrich
H
Aszódi
András
A
Stuetz
Anton
A
D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine; D016559:Tacrolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D016559:Tacrolimus