PHARMACOKINETICS OF (-)-NOREPHEDRINE, (-NOREPHEDRINE AND (+() )-)-NOREPHEDRINE - PLASMA-CONCENTRATIONS, SERUM-PROTEIN BINDING AND URINARY EXCRETIONS/

The pharmacokinetics of norephedrine enantiomers were determined after the independent i.v. administration of (+/-)-norephedrine (20 mg/kg), (-)-norephedrine (10 mg/kg), and (+)-norephedrine (10 mg/kg) to rats. Significant differences were observed in the pharmacokinetic paramete rs of each enantiomer when the enantiomers were administered singly an d as a racemate. For example, the values of total body clearance (Clto t) and urinary excretion clearance (Clr) of (-)-norephedrine administe red as a racemate were higher than those of the norephedrine enantiome r administered singly. The areas under the curve of concentration vers us time (AUC) of (-)-norephedrine administered as a racemate had a ten dency to increase. While Cltot of (+)-norephedrine administered as a r acemate showed a lower value and A UC showed a higher value. The value of Clr of (+)-norephedrine administered as a racemate showed a tenden cy to decrease. There was no difference in the in vitro serum protein binding of (-)- and (+)-norephedrine. The data from this study reveal that pharmacokinetic interactions exist between the norephedrine enant iomers and also reveal that the serum protein binding is not concerned with those interactions. The differences in the pharmacological effec ts after the individual administration of (-)-norephedrine or (+)-nore phedrine may be coused by the differences in their concentrations in t he plasma.