Relative bioavailability of carbinoxamine and phenylpropanolamine from a retard suspension after single dose administration in healthy subjects.

The plasma pharmacokinetics of carbinoxamine (CA, CAS 486-16-8) and phenylpropanolamine (PP, CAS 14838-15-4) after single dose administration of a retard suspension (Rhinopront), containing a resinate as sustained-release agent, were compared to those of the same active principles given as an aqueous solution. The study was performed in 20 healthy subjects who received the two formulations according to a standard crossover design with a one-week wash-out. Blood samples were obtained up to 24 h post-dose. PP and CA were assayed in the plasma samples by gas chromatography with electron-capture detection and HPLC with coulometric detection, respectively. The pharmacokinetic results indicated sustained release of the two active principles with the retard suspension: CA appeared in plasma at a much slower rate than with the solution, a 30% lower Cmax being reached after 8.0 h instead of 3.0 h post-dose. For PP, Cmax was 23% lower and occurred 3.0 post-dose instead of 1.5 h with the solution. The extent of absorption of the two drugs, as assessed by AUC (0-24 h), was slightly smaller with the retard suspension than with the aqueous solution. However, the test/reference ratio remained within 95% confidence intervals of 80-87% and 88-98% for CA and PP, respectively, indicating bioequivalence of the two formulations. A simulation of the plasma levels during repeated administration indicated that dosing with the retard suspension at 12-h intervals should yield the same steady-state plasma levels as a 5 times daily administration of a divided dose of the aqueous solution, for both drugs.