Pharmacokinetics of pheniramine (Avil) and metabolites in healthy subjects after oral and intravenous administration.

ABSTRACT

The pharmacokinetics of pheniramine and its two metabolites (N-desmethyl pheniramine and N-didesmethyl pheniramine) were determined in six healthy male subjects after intravenous (n = 3) or oral (n = 3) administration (30.5 mg of pheniramine - free base). Serum and urine levels were measured by HPLC. After i.v. administration, serum concentrations of pheniramine between 231 and 894 ng/ml were reached and after oral administration peak serum concentrations between 173 and 274 ng/ml were reached after 1-2.5 h. AUC values up to 72 h were 3035-4662 (i.v.) and 3507-5768 (ng/ml X h) (oral). The terminal half-lives were estimated to range between 8 and 17 h (i.v.) and 16 and 19 h (oral). Serum levels of the N-desmethyl derivative remained very low (up to 21 ng/ml), but were still detectable after 72 h. Serum levels of the N-didesmethyl derivative were below the detection limit. The amount of pheniramine excreted in the urine for up to 120 h varied between 5.7 and 11.6 mg and 10.2 and 13.2 mg after i.v. and oral administration respectively. Unlike the serum, considerable fractions of the drug occurred as metabolites in urine. Values were 8.1-16.4 mg (i.v.) and 7.4-13.3 mg (oral) for N-desmethyl pheniramine, 0.4-2.9 mg (i.v.) and 0.2-0.8 mg (oral) for N-didesmethyl pheniramine.