ABSTRACT
Development of a toxicology evaluation plan for a transdermal system involves two major stages: assessment of previous experience with the drugs and the system components and selection of necessary and appropriate studies. This chapter discusses development of an evaluation plan for a transdermal dosage form and the various toxicology tests available with a focus on irritation and sensitization tests. For transdermal product development, information about oral or intravenous administration provides a basis for comparison and may be used to support the safety and efficacy of transdermal delivery when equivalent plasma levels are achieved and no significant biotransformation occurs. Toxicokinetic analysis is increasingly important in nonclinical toxicology protocols for transdermal and other dosage forms and is included in guidelines drafted by the International Conference on Harmonization. Skin metabolism may alter the delivery profile and pharmacological effects of some percutaneously absorbed compounds. The toxicology profile of compounds may be altered by the quantitative modification of metabolic pathways caused by skin metabolism.
