RELATIVE BIOAVAILABILITY OF CARBINOXAMINE AND PHENYLEPHRINE FROM A RETARD CAPSULE AFTER SINGLE AND REPEATED DOSE ADMINISTRATION IN HEALTHY-SUBJECTS

The plasma pharmacokinetics of carbinoxamine (CA, CAS 486-16-8) and phenylephrine (PE, CAS 59-42-7) after single dose administration of a retard capsule (Rhinopront(R)) containing 20 mg PE hydrochloride and 4 mg CA maleate, were compared to those of the same active principles given as an aqueous solution. The study was performed in 20 healthy subjects according to a standard crossover design with a one-week wash-out. The pharmacokinetic profile of the active ingredients of the retard capsule was also investigated in the same subjects under repeated dosing conditions (one capsule bid during 4 days). Blood samples were collected before each administration and up to 36 h after the first and last doses CA and total PE (free + conjugated) weve assayed in the plasma samples by HPLC with coulometric detection and by gas chromatography with electron-capture detection, respectively. The pharmacokinetic parameter obtained after single dose administration indicated an effective slow release of PE and CA with the retard capsule, compared to the solution. Significantly dampened C-max, delayed t(max), and prolonged plateau time were observed. Despite the clear decrease in absorption rate, the two formulations yielded a similar extent of absorption for CA (90 % confidence interval of AUC ratio. 61-111 %), but not for PE (90 % confidence interval of AUC ratio: 56-69 %). At steady-state, accumulation of the two active principles apparently followed simple superposition (accumulation index R = 1.6 for PE and 3.9 for CA). The slow absorption pattern of the formulation was maintained at steady-state with t(max) and plateau time similar to single dose conditions.