Phenylpropanolamine pharmacokinetics in dogs after intravenous, oral, and oral controlled-release doses

An adaption of a published high performance liquid chromatographic (HPLC) assay for phenylpropanolamine (PPA) in plasma was used to examine PPA pharmacokinetics in dogs. Plasma was extracted into ethyl acetate after the addition of 3.5 per cent sodium carbonate, and was then back-extracted into aqueous acetic acid. The acetic acid was injected onto a cyano column using a mobile phase of acetonitrile, dilute hydrochloric acid, and sodium heptane sulfonate. Detection was by UV absorbance at 210 nm. The relative standard deviation of replicate assays averaged 5.2 per cent over a concentration range of 50-1750 ng ml-1 plasma. PPA extraction recovery exceeded 90 per cent. The limit of detection was 30 ng ml-1 using 0.5 ml plasma and injecting 10 microliter. PPA disposition was characterized in three dogs administered PPA i.v. and orally in immediate-release and controlled-release formulations. The terminal elimination half-life averaged 3.5 +/- 0.5 h after the i.v. dose. Oral absorption from the immediate-release capsule was rapid and bioavailability was 98.2 +/- 6.9 per initial rapid cent. PPA absorption from the controlled-release dosage form was biphasic; an rapid phase was followed by a second, slower absorption phase which continued over 16 h. Plasma PPA concentrations then declined with a half-life roughly parallel to the i.v. and oral immediate-release half-lives. Oral bioavailability from the controlled release tablet was 93.7 +/- 5.9 per cent.