Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
+44-20-4587-4809
ISSN: 2157-7609
+44-20-4587-4809
S. R. Meier-Davis
1718 Ringwood Avenue, San Jose, CA 95131,
Canada
Research Article
Comparison of Metabolism of Donepezil in Rat, Mini-Pig and Human, Following Oral and Transdermal Administration, and in an In Vitro Model of Human Epidermis
Author(s): S. R. Meier-Davis, R. Murgasova, C. Toole, F. M. Arjmand, L. Diehl, B. Cayme, J. Wen, J. Shudo and T. NagataS. R. Meier-Davis, R. Murgasova, C. Toole, F. M. Arjmand, L. Diehl, B. Cayme, J. Wen, J. Shudo and T. Nagata
Donepezil hydrochloride is a centrally acting, reversible acetyl cholinesterase inhibitor approved for Alzheimer’s disease therapy. Donepezil is marketed as an oral tablet but a transdermal patch may have advantages as an alternate therapy. To determine whether the transdermal route alters known donepezil metabolism, this study compared plasma metabolites of donepezil hydrochloride with two routes of drug delivery, transdermal and oral, in three species; rat, mini-pig and human. The utility of a reconstituted human epidermis (RHE) in vitro model for transdermal drug biotransformation was also evaluated. In addition to donepezil, structures from three metabolic pathways were detectable in each matrix: 1) O demethylation (M1/M2; 2) N-dealkylation (M4); 3) N-oxidation (M6) utilizing LC/quadrupole–Ion trap MS/MS. In rats and humans, including RHE, the mean con.. View More»
DOI:
10.4172/2157-7609.1000129