caa a22 4500 477125638 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970101xx s 000 0 eng 10.1023/A:1012051300130 doi (NATIONALLICENCE)springer-10.1023/A:1012051300130 Selegiline Percutaneous Absorption in Various Species and Metabolism by Human Skin [Elektronische Daten] [Shashank Rohatagi, Jeffrey Barrett, Lee McDonald, Esther Morris, John Darnow, Anthony DiSanto] Purpose. A Selegiline Transdermal System (STS) is under development for indications which may not be optimally or safely treated with oral selegiline. Studies were conducted to evaluate the in vitro penetration and skin metabolism of selegiline in order to better understand the toxicological findings and the observed plasma levels of selegiline and its metabolites in animals and man. Methods. In vitro penetration studies were conducted in four different species (male hairless mice, male and female rats, female dog and male Micropig® and compared to human skin. In another study, viable human skin was used to estimate the extent of metabolism of selegiline by human skin using Franz diffusion cells. Results. Results indicated that female dog and male Micropig® skin were reasonable animal models for 24 hour in vitro selegiline penetration through human skin. Penetration of selegiline through rat skin and hairless mouse skin was 2-fold and 3-fold higher than through human skin, respectively. Metabolism was negligible in human skin. Selegiline metabolites (L-methamphetamine and N-desmethylselegiline but not L-amphetamine) were detected at all time points but the extent of selegiline metabolism was negligible. The cumulative 24 hour in vitro selegiline permeation from a 1.83 mg/cm2 STS through human skin was 5.0 mg. This was similar to the in vivo permeation in humans as assessed by residual patch analysis. Conclusions. The similarity of dog and human skin permeation results support the use of the dog as a species for evaluating the toxicology of transdermally-administered selegiline. Selegiline is not metabolized cutaneously and hence the metabolic profile following STS administration is likely due to hepatic metabolism only. Plenum Publishing Corporation, 1997 skin permeation nationallicence metabolism nationallicence selegiline nationallicence transdermal nationallicence Rohatagi Shashank Somerset Pharmaceuticals, Tampa, Florida aut Barrett Jeffrey Somerset Pharmaceuticals, Tampa, Florida aut McDonald Lee IIT Research Institute, Chicago, Illinois aut Morris Esther Bushy Run Research Center, Export, Pennsylvania aut Darnow John Somerset Pharmaceuticals, Tampa, Florida aut DiSanto Anthony Somerset Pharmaceuticals, Tampa, Florida aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 50-55 0724-8741 14:1<50 1997 14 11095 https://doi.org/10.1023/A:1012051300130 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012051300130 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rohatagi Shashank Somerset Pharmaceuticals, Tampa, Florida aut NATIONALLICENCE 700 1- Barrett Jeffrey Somerset Pharmaceuticals, Tampa, Florida aut NATIONALLICENCE 700 1- McDonald Lee IIT Research Institute, Chicago, Illinois aut NATIONALLICENCE 700 1- Morris Esther Bushy Run Research Center, Export, Pennsylvania aut NATIONALLICENCE 700 1- Darnow John Somerset Pharmaceuticals, Tampa, Florida aut NATIONALLICENCE 700 1- DiSanto Anthony Somerset Pharmaceuticals, Tampa, Florida aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 50-55 0724-8741 14:1<50 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer