Steady-state kinetics of sustained-release phenylpropanolamine

The plasma concentrations and the urinary excretion of phenylpropanolamine were studied in eight healthy volunteers during a dose interval in steady state after intake of a sustained-release preparation of the drug (Rinexin, AB Leo). The plasma and urine levels were determined by a gas chromatographic method using electron capture detection, with a detection limit of about 10 ng/ml. The sustained-release action of the dosage form was consistent in all subjects, with a flat plasma concentration-time profile between 2 and 8 h after dose intake. Cmax was 167 +/- 28 ng/ml (mean +/- SD) and Cmin 59 +/- 19 ng/ml. The terminal plasma half-life was 5.6 +/- 1.0 h, total body clearance 0.57 +/- 0.14 l/kg/h, Vdarea 4.4 +/- 1.2 l/kg, and the fraction excreted unchanged in the urine 86 +/- 13%. In conclusion, phenylpropanolamine was found to be a high clearance drug characterized by extensive renal elimination of unchanged drug. The plasma levels showed only small interindividual variations in our healthy volunteers. Caution should be taken in treating patients with impaired renal function.