Direct measurement of propranolol bioavailability during accumulation to steady-state.
1. A high performance liquid chromatographic method for the determination of propranolol in human plasma and blood has been developed and used to confirm that cumulation occurred during chronic oral administration, steady-state being achieved within 48 h of beginning 80 mg of the drug every 8 h. 2. The method was adapted to measure [H3]-propranolol and native drug in the same blood sample and was applied to determine simultaneously the disposition of i.v. ([H3]-propranolol) and orally (non-labelled) administered drug after single oral dose of 80 mg and when steady-state had been established on an 80 mg, 8-hourly regimen. 3. Using this approach it was possible to show that a reduced oral clearance at steady-state was associated with a smaller reduction in systemic (i.v.) clearance and no change in liver blood flow. A direct estimate of bioavailability was also possible and was found to be increased at steady-state compared with a single oral dose. 4. We conclude that the accumulation of propranolol during the attainment of steady-state is due to a reduction in intrinsic clearance, resulting in reduced presystemic hepatic extraction.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D011433:Propranolol