Comparative pharmacokinetics and distribution kinetics in brain of phencynonate enantiomers in rats

To investigate the pharmacokinetics in blood and the distribution kinetics in brain of enantiomers of novel anticholinergic agent phencynonate (N-methyl-9α-(3-azabicyclo[3,3,1]nonanyl)-2′-cyclopentyl-2′-hydroxyl-2′-phenylacetate), we collected blood and implanted microdialysis probes in the cerebral frontal cortex of rats. Phencynonate enantiomers (0.35 mg/kg, i.m.) were then cross administered, and the microdialysates were collected using in situ microdialysis sampling in the brain of freely moving rats, and the concentration of phencynonate enantiomers was determined by the validated method of liquid chromatography–mass spectrometry. Pharmacokinetic parameters were calculated from the blood and the brain dialysate concentrations of phencynonate enantiomers versus time data. The disposition profiles of the phencynonate enantiomers were best fitted to a first order absorption, two-compartment open model in rats. In general, there were some differences when comparing the mean kinetic parameters of S- and R-phencynonate in the blood and brain, but the distinct diversity between individual animals made the statistical difference not obvious. Therefore, stereoselective disposition of phencynonate isomers was not obviously observed in rat.