Abstract
The absorption, distribution, metabolism and excretion of Betaxolol were investigated in male and female rats after oral or intravenous administration of 14C-Betaxolol.
1. After oral administration of 14C-Betaxolol to male rats, there was a good correlation between the area under time versus concentration curve(AUC0→∞) of radioactivity in blood and administered doses ranging from 0.5 to 5mg/kg.
2. After intravenous administration (1 mg/kg) of 14C-Betaxolol to male rats, blood levels of radioactivity decreased rapidly until 30min after dosing, and then increased until 1hr after dosing, followed by the decrease with half-lives of 2.2hr and 21.9hr. Plasma levels of unchanged betaxolol decreased rapidly with half-lives of 0. 28hr (T1/2α) and 1.18hr (T1/2β).
3. After oral administration (5mg/kg) of 14C-Betaxolol to male and female rats, blood levels of radioactivity reached the maxima at 1hr and decreased with half-lives of 1. 52hr and 20. 3hr in male rats, and 1. 34hr and 17. 9hr in female rats, respectively. Plasma levels of unchanged Betaxolol of female rat were significantly higher than those of male rat. The systemic bioavailability in male rats was 7.9%.
4. Radioactivity was excreted completely in urine (83.1%) and feces (15.0%) within 96hr after oral administration to male rats. Cumulative biliary excretion rate of radioactivity was 5. 6% of the dose within 48hr after oral administration.
5. Radioactivity in most tissues reached the maxima at 0.5 or 1hr after oral administration. The tissue levels of radioactivity were higher in the liver, intestinal tract, kidney, lung, adrenal and submaxillary gland than in plasma, and then decreased with the halflives similar to radioactivity in blood.
6. Main metabolite in plasma, urine, feces and organs (liver, kidney, heart and brain) was M-1. Major metabolic route of Betaxolol in rats was oxidation of cyclopropylmethoxyethyl moiety.
