Premium
Propranolol stereoisomer plasma concentrations and portal haemodynamic response in patients with liver cirrhosis
Author(s) -
Michael Schepke,
Peter Raab,
Alexander Hoppe,
Karl August Brensing,
D. Paar,
U. Potyka,
Tilman Sauerbruch
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00622.x
Subject(s) - propranolol , portal hypertension , cirrhosis , hemodynamics , medicine , portal venous pressure , stereoselectivity , endocrinology , chemistry , biochemistry , catalysis
Background : The haemodynamic effect of propranolol on portal pressure in patients with portal hypertension is highly variable and does not correlate with propranolol racemate plasma concentrations. Aim : To investigate the stereoselective metabolism of the propranolol enantiomers and its impact on portal haemodynamics in patients with liver cirrhosis since only S‐propranolol is haemodynamically active. Methods : Twenty patients with liver cirrhosis and portal hypertension received 40 mg propranolol orally. Portal blood velocity (PBV) and propranolol stereoisomer plasma concentrations were determined. Results : During the 4 h examination period we observed a significant reduction in PBV (18.3 ± 2.2%, P < 0.0001) vs. baseline. The area under the curve ( AUC ) during the study period was significantly different for the two isomers (S‐propranolol 1217.0 ± 118.5 nmol.h/L; R‐propranolol 728.8 ± 103.8 nmol.h/L, P < 0.0001). Seven patients (35%) were portal haemodynamic non‐responders to propranolol. Propranolol stereoisomer AUC values were no different between responders (S‐propranolol 1133.3 ± 132.0 nmol.h/L; R‐propranolol 718.0 ± 129.7 nmol.h/L) and non‐responders (S‐propranolol 1371.8 ± 250.5 nmol.h/L; R‐propranolol 746.9 ± 200.3 nmol.h/L); neither was there a correlation between propranolol enantiomer plasma concentrations and the portal haemodynamic effect. Conclusions : Our data demonstrate a stereoselective metabolism of propranolol enantiomers in liver cirrhosis. However, following oral propranolol administration, stereoisomer plasma concentrations do not predict the portal haemodynamic effect.