Serum concentrations of phenylpropanolamine and associated effects on blood pressure in normotensive subjects: a pilot-study.

This study was undertaken to investigate the effects of racemic phenylpropanolamine (PPA) on blood pressure (BP) in normotensive human subjects following the administration of three different dosages of PPA (25 mg, 50 mg and 100 mg) as single doses and to determine whether any relationship existed between the serum concentrations of PPA and its possible effects on BP. Blood was sampled and BP measured at specified times. Phenylpropanolamine was determined by HPLC with UV detection. No significant changes in BP occurred following the 25 mg dose (5 +/- 7/6 +/- 6 mm Hg), whereas statistically significant changes were found after the two higher doses of 50 mg (26 +/- 16/12 +/- 13 mm Hg) and 100 mg (30 +/- 13/15 +/- 8 mm Hg). Increases in systolic pressure following the 50 mg and 100 mg doses appeared to show a better correlation with peak serum concentrations of PPA than did diastolic effects. Although serum concentrations of PPA increased linearly with increasing dose, no clear-cut correlation could be found between serum concentrations and BP effects. The pressor effects, however, became more noticeable following the 50 mg dose and were markedly increased following the 100 mg dose. Side-effects which were reported were relatively minor even at the higher doses.

Steady state pharmacokinetics and dose-proportionality of phenylpropanolamine in healthy subjects.

The pharmacokinetics of phenylpropanolamine (PPA) were studied in five healthy male volunteers after single oral doses of 25, 50 and 100 mg of the drug as well as at steady state after seven, 4-hourly doses of PPA. The peak serum concentrations and AUC infinity values increased linearly with an increase in dose, whereas the time to reach peak serum concentrations did not vary significantly between doses. The half-life remained relatively constant with an increase in dose (t1/2 = 3.8 to 4.3 hours), as did renal clearance (ClR = 0.41 to 0.44 l/kg/h). The percentage of unchanged PPA excreted in the urine over a 14 hour period was 64%, 63% and 73% for the 25, 50 and 100 mg doses, respectively. The pharmacokinetics of PPA were found to be linear in the dosage range 25 to 100 mg. Steady state serum concentrations were significantly higher than single dose concentrations, with the mean peak serum concentration increasing from 113 ng/ml after a single dose to 183 ng/ml at steady state. The time at which these were attained decreased from 1.47 hours after a single dose to 0.73 hours at steady state. Both clearance and volume of distribution were significantly different after a single dose compared to steady state (P less than 0.05), whereas no significant differences were found between the other parameters.