Individual variability in the blood pressure response to intravenous phenylpropanolamine: a pharmacokinetic and pharmacodynamic investigation

Abstract

The intersubject variability in blood pressure response to 0.44 mg/kg intravenous phenylpropanolamine (d,l-norephedrine) was studied in 10 normal subjects. A phenylpropanolamine or placebo infusion was administered over 45 minutes on separate days according to a double-blind, balanced protocol. Blood pressure increased by 24 +/- 13/16 +/- 7 mm Hg (systolic/diastolic, mean +/- SD) after the phenylpropanolamine infusion and was statistically different from the placebo infusion response (7 +/- 5/8 +/- 3 mm Hg). Phenylpropanolamine infusions were terminated early in two subjects (hyperresponders) after 0.31 and 0.23 mg/kg because of excessive increases in blood pressure (52/30 and 34/21 mm Hg, respectively). The hyperresponders had the lowest peak serum phenylpropanolamine concentrations. These data suggest that considerable intersubject variability exists in the blood pressure response to intravenous phenylpropanolamine. A pharmacokinetic basis for the variability in response to racemic phenylpropanolamine was not observed. A relationship did not exist within the group between blood pressure effect and serum concentration but did exist within each subject. Therefore phenylpropanolamine's blood pressure effect in an individual cannot be predicted solely from a serum concentration of racemic drug.