[Pharmacokinetics of (-)-, (+)- and (+/-)-norephedrine. Plasma concentrations, serum protein binding and urinary...

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 parameters of each enantiomer when the enantiomers were administered singly and as a racemate. For example, the values of total body clearance (Cltot) and urinary excretion clearance (Clr) of (-)-norephedrine administered as a racemate were higher than those of the norephedrine enantiomer administered singly. The areas under the curve of concentration versus time (AUC) of (-)-norephedrine administered as a racemate had a tendency to increase. While Cltot of (+)-norephedrine administered as a racemate showed a lower value and AUC showed a higher value. The value of Clr of (+)-norephedrine administered as a racemate showed a tendency 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 enantiomers and also reveal that the serum protein binding is not concerned with those interactions. The differences in the pharmacological effects after the individual administration of (-)-norephedrine or (+/-)-norephedrine may be coused by the differences in their concentrations in the plasma.