Azathioprine transport through rat skin and its immunosuppressive effect.
The objective of this research was to study the in vitro and in vivo percutaneous absorption of azathioprine with and without the effect of penetration enhancers. In vitro permeation of azathioprine was studied using a Franz diffusion cell and rat skin. Both azathioprine and 6-mercaptopurine were detected in the receiver solution with a reversed phase HPLC system. The steady state flux of azathioprine, permeability coefficient, and lag time were reported. Penetration enhancers such as dimethylsulfoxide (DMSO), dimethylformamide (DMF), and urea were added to the donor compartment to increase the skin permeation of azathioprine. The flux of azathioprine was increased by 20.7%, and 22.4% using dimethylsulfoxide, and dimethylformamide respectively. The in vivo permeation was determined by measurement of antibody titers by the slide latex agglutination test. The in vivo permeation study showed that the titers of antibody induced in the rats were not affected by topical application of azathioprine solution. The results show that azathioprine has low flux to exert a systemic effect with and without penetration enhancers. However these results may support the use of topical azathioprine for the treatment of some dermatological disorders with minimum side effects.
Tashtoush
B M
BM
Department of Pharmaceutical Technology, College of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan. bmtash@just.edu.jo
Al-Safi
S A
SA
Al-Fanek
K J
KJ
D000465:Algorithms; D000818:Animals; D001379:Azathioprine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D066298:In Vitro Techniques; D015122:Mercaptopurine / Q000493:pharmacokinetics; D010539:Permeability; D051381:Rats; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine