Effect of vitamin K3 on the first-pass elimination of propranolol in the rat

The effect of vitamin K3, which inhibits electron transfer from NADPH to cytochrome P-450 via cytochrome c reductase, on the metabolism of propranolol was studied in the rat in vitro and in vivo. For in vitro experiments using rat liver microsomes, the metabolism of propranolol was inhibited by vitamin K3. For in vivo experiments, the area under the blood concentration-time curve and the maximum concentration of propranolol were markedly increased following intraportal infusion of propranolol with vitamin K3, but intraportal administration of vitamin K3 had little effect on propranolol kinetics when propranolol was infused intravenously. Thus, it was concluded that vitamin K3 inhibited the first-pass metabolism of propranolol.