EFFECT OF DOSE OF METOPROLOL ON ITS ELIMINATION BY ISOLATED-PERFUSED RAT-LIVER IN-VITRO

The effects of dose of metoprolol (Met) on hepatic elimination was stu died in isolated rat liver perfused at a flow of 25 ml . min-1. The re sults showed that Met was eliminated by rat liver in accordance with o ne-compartment model. Linear kinetic eliminating processes (apparent f irst-order kinetics) were found in doses of Met 0. 2, 0. 5, 1. 0, and 2. 0 mg , T1/2 were 8. 3, 8. 8, 9. 6, and 10.6 min and the clearance r ate were 11. 7, 11. 8, 9. 6, and 8. 6 ml . min-1, respectively. Nonlin ear eliminating pocesses were found in doses of Met 4, 8, and 12 mg . V(m )and K(m) were 0. 98, 1.05, and 0. 94 mug . min-1 . ml-1 and 15. 6 , 16. 9, and 14. 6 mug . ml-1, respectively. It is concluded that hepa tic Met elimination is independent on lower doses, but rested upon hig h doses.