Studies on the metabolic fate of (.+-.)-1-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)-3-isopropylamino-2-propanol hydrochloride (betaxolol hydrochloride). (2): Blood level profiles, distribution, metabolism, excretion, aecumulation and effects on the hepatic drug-metabolizing enzyme activities of betaxolol after repeated oral administration to rats.

Abstract

The absorption, distribution, metabolism, excretion and accumulation of Betaxolol were investigated after repeated oral administration of 14C-Betaxolol (5mg/kg/day) to male rats for 21 days. The effect of Betaxolol on the hepatic drug-metabolizing enzyme activities was also investigated after repeated oral administration of Betaxolol (5 and 20mg/kg/day) to male rats for 21 days.1. Blood levels of radioactivity at 2hr after each dosing remained almost constant since the 1st day. During the repeated oral administration of 14C-Betaxolol, blood levels of radioactivity at 24hr after each dosing continued to increase till the 14th day. After the 14th administration, blood levels of radioactivity reached to the plateau. Blood levels of radioactivity after repeated oral administration decreased more slowly than that after a single administration.2. The excretion rates of radioactivity in the urine and feces were nearly constant during the period of repeated administration of 14C-Betaxolol, and were similar to those after a single administration. Within 24hr after the last dosing, 80% of the administered radioactivity was recovered in urine and 18.8% in feces.3. The tissue levels of radioactivity at 24hr after each dosing increased gradually until the 14th administration, followed by remaining of almost same level. The tissue levels of radioactivity after 21 days repeated administration decreased gradually.4. The percentages of unchanged Betaxolol and metabolites to radioactivity in plasma, tissues (liver, kidney and heart) and urine after repeated administration were almost same as those after a single administration.5. Betaxolol had no effect on the hepatic drug-metabolizing enzyme system.