DISPOSITIONAL FACTORS DO NOT CONTRIBUTE TO THE ENANTIOSPECIFICITY OF THE CARDIOVASCULAR EFFECTS OF PHENYLPROPANOLAMINE

The pharmacokinetics and blood pressure response of the phenylpropanolamine enantiomers (i.e., d- and l-phenylpropanolamine) were determined after the separate oral administration of racemic dl-phenylpropanolamine (75 mg), l-phenylpropanolamine (37.5 mg), and d-phenylpropanolamine (37.5 mg) to six healthy volunteers. No significant differences were observed between any of the pharmacokinetic parameters of d- and l-phenylpropanolamine when the enantiomers were administered individually or as the racemate. There was also no difference in the ex vivo plasma protein binding of d- and l-phenylpropanolamine, determined individually or as the racemate. Significant increases from baseline in systolic and diastolic blood pressure (supine and standing) were observed for dl- and l-phenylpropanolamine, whereas d-phenylpropanolamine had no effect on blood pressure. The effects of dl- and l-phenylpropanolamine on blood pressure were not significantly different. The data from this study show that pharmacokinetic factors do not contribute to the stereospecificity of the cardiovascular effects of phenylpropanolamine or to the interindividual variability in the blood pressure response to phenylpropanolamine.