A comparative study of the pharmacokinetics of propranolol and its major metabolites in the rat after oral and vaginal administration

Abstract

1. The concentrations of propranolol (PPL) and its metabolites were monitored by h.p.l.c. in serum of rats during the first 6 h after administering single doses (20 mg/kg) of PPL either orally or intravaginally (i.vg).

2. The results showed that PPL was quickly transferred to the systemic circulation from the rat vagina and the serum concentration profile as substantially altered by the route of administration. Serum concentrations of free PPL were significantly higher in i.vg-dosed animals than their oral dosed counterparts.

3. Inter-animal serum conc. variations of PPL and its metabolites in the i.vg-dosed rats were smaller than those of the orally treated females.

4. In comparison with the i.vg-dosed rats, the levels of PPL metabolites (propranolol glycol, naphthoxylactic acid, naphthoxyacetic acid) were greater by the oral route, though these differences were not statistically significant.

5. The serum elimination half-lives (t_1/2)_β of PPL and its metabolites during the β-phase were not significantly different in the two treatment groups.

6. Following i.vg application, both the AUC and the C_max values of PPL were significantly greater than those of orally dosed females, while no statistically significant differences were found in the t_max values.

7. Comparison of the AUC values showed that relative bioavailability of PPL was approx. 36 times greater in i.vg-treated animals than those of the orally dosed rats.