Propranolol stereoisomer plasma concentrations and portal haemodynamic response in patients with liver cirrhosis

Abstract

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 nmoI.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 nonresponders (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.