1. Zamifenacin was rapidly metabolized in vitro by liver microsomes fr
om rat, dog, and man. 2. Zamifenacin exhibited extensive plasma protei
n binding with human plasma showing 20 and 10-fold higher binding that
that in rat and dog respectively. 3. Following oral administration to
animals, metabolic clearance resulted in decreased bioavailability du
e to first-pass metabolism in rat and mouse. Oral clearance in man was
low as a result of increased metabolic stability and increased plasma
protein binding compared with animals. 4. Metabolism was the major ro
ute of clearance of zamifenacin with the primary metabolic step result
ing in opening of the methylenedioxy ring to yield the catechol. In ma
n, this metabolite was excreted as the grucuronide conjugate, whereas
in the animal species it was further metabolized by mono-methylation o
f the catechol.