Partial metabolic clearances as determinants of the oral bioavailability of propranolol

British Journal of Clinical Pharmacology
T WalleE C Conradi

Abstract

The objective of this study was to determine the relationships between the total oral clearance of propranolol and the partial clearances through its primary metabolic pathways, i.e. glucuronidation, side-chain oxidation and ring oxidation. Seven young, white males were given single 80 mg oral doses of the drug together with tritium-labelled propranolol. Plasma propranolol was measured by GC/MS and fourteen metabolites were measured in urine by h.p.l.c. with radiometric detection. The total oral clearance of propranolol in these subjects varied about three-fold, from 27.5 to 71.4 ml min-1 kg-1. The clearance through glucuronidation was very similar in all subjects, ranging from 6.8 to 9.9 ml min-1 kg-1. The clearance through side-chain oxidation varied 2.4-fold, from 10.9 to 25.8 ml min-1 kg-1. Increased clearance through this pathway correlated with increased total oral clearance (r = 0.84; P less than 0.02). The clearance through ring oxidation varied as much as 5.6-fold, from 7.5 to 41.8 ml min-1 kg-1. Increased clearance through this pathway correlated highly with increased total oral clearance (r = 0.94; P less than 0.002). These observations indicate that the intersubject variability in the oral clearance of propranolol i...Continue Reading

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Citations

Nov 7, 2001·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·J L DorneA G Renwick
Mar 1, 1992·British Journal of Clinical Pharmacology·U M BirgersdotterD M Roden
Mar 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·T WalleT E Gaffney
Aug 1, 1989·Journal of Clinical Pharmacology·J T WilsonA Whelton
Jan 1, 1988·Biochemical Pharmacology·T WalleT E Gaffney
Jul 1, 1995·Biopharmaceutics & Drug Disposition·B TrauschT Gramatté
Aug 8, 1998·Clinical Pharmacology and Therapeutics·C von BahrJ Gabrielsson
Aug 2, 2017·Advanced Pharmaceutical Bulletin·Ebrahim SalehifarPouneh Ebrahimi
Apr 14, 2017·CNS Drugs·Peer Tfelt-HansenJacob Tfelt-Hansen

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