PT - JOURNAL ARTICLE AU - H H Chow AU - D Lalka TI - The influence of vitamin K3 treatment on the pharmacokinetics and metabolism of (+)-propranolol in the rat. DP - 1992 Mar 01 TA - Drug Metabolism and Disposition PG - 288--294 VI - 20 IP - 2 4099 - http://dmd.aspetjournals.org/content/20/2/288.short 4100 - http://dmd.aspetjournals.org/content/20/2/288.full SO - Drug Metab Dispos1992 Mar 01; 20 AB - The effects of vitamin K3 treatment on the pharmacokinetics and metabolism of (+)-propranolol and the consequences of hepatic injury associated with vitamin K3 treatment were examined in groups of male Sprague-Dawley rats. When vitamin K3 (20 mg/kg) in polyethylene glycol 300 (PEG 300) was coinfused with (+)-propranolol (2 mg/kg) into the pyloric vein (a tributary flowing directly into the hepatic portal vein), a significant decrease in the intrinsic clearance of total drug (CLint) from 94.1 +/- 50.1 to 32.9 +/- 11.5 ml/min/kg was observed (p less than 0.01 vs. vehicle control). However, a lower dose of vitamin K3 (2 mg/kg in PEG 300) had little effect on this parameter. Interestingly, the PEG 300 vehicle control group exhibited a significantly (p less than 0.05) higher CLint than that observed in a saline control group (94.1 +/- 50.1 vs. 45.9 +/- 13.7 ml/min/kg). This difference appeared to be due to an increase in the free fraction of propranolol caused by PEG 300, because in vitro addition of this solvent to serum (at estimated in vivo concentrations) with or without added vitamin K3 doubled propranolol free fraction. Furthermore, rats that received the high dose vitamin K3 (20 mg/kg) treatment exhibited a pronounced increase in the serum concentration of enzymes of hepatic origin (alanine aminotransferase and sorbitol dehydrogenase) and in the incidence of hepatic necrosis. It was also observed that high-dose vitamin K3 treatment caused only minor changes in the urinary recovery of propranolol metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)