Variable first-pass elimination of propranolol following single and multiple oral doses in hypertensive patients

The disposition of orally administered propranolol has been studied in twelve patients with mild to moderate hypertension. Each patient received single doses of 40, 80, and 160 mg. Serial blood samples were obtained and quantitated using a sensitive gas chromatographic analytical technique. Ten of t...

Full description

Saved in:
Bibliographic Details
Published in:European journal of drug metabolism and pharmacokinetics 1982-01, Vol.7 (3), p.183-189
Main Authors: Wargin, W A, Sawchuk, R J, McBride, J W, McCoy, H G, Rylander, M L
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Biological Availability
Chromatography, Gas
Half-Life
Humans
Hypertension - drug therapy
Kinetics
Middle Aged
Propranolol - administration & dosage
Propranolol - metabolism
Propranolol - therapeutic use
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The disposition of orally administered propranolol has been studied in twelve patients with mild to moderate hypertension. Each patient received single doses of 40, 80, and 160 mg. Serial blood samples were obtained and quantitated using a sensitive gas chromatographic analytical technique. Ten of the twelve patients received 40 mg doses of propranolol every 6 hours for 5 doses. Blood samples were obtained after administration of the first, second, third, and fifth doses. Substantial intersubject variability in the areas under the bloodconcentration-time profiles (AUC) was observed. Evidence for a nonlinear first-pass effect was not obtained in all patients. The patients displaying a nonlinear relationship between dose and AUC for single propranolol doses consistently showed a similar relationship during multiple dosing. Blood levels obtained following the evening dose (08h00 to 14h00) appeared to be lower than expected based on multiple-dosing pharmacokinetic principles. These findings suggest that monitoring propranolol blood levels is the most viable way to ascertain therapeutic concentrations of this drug.
ISSN:0378-7966
2107-0180
DOI:10.1007/BF03189564