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

Background: The haemodynamic effect of propranolol on portal pressure in pa tients with portal hypertension is highly variable and does not correlate w ith propranolol racemate plasma concentrations. Aim: To investigate the stereoselective metabolism of the propranolol enant iomers and its impact on portal haemodynamics in patients with liver cirrho sis since only S-propranolol is haemodynamically active. Methods: Twenty patients with liver cirrhosis and portal hypertension recei ved 40 mg propranolol orally. Portal blood velocity (PBV) and propranolol s tereoisomer plasma concentrations were determined. Results: During the 4 h examination period we observed a significant reduct ion in PBV (18.3 +/- 2.2%, P < 0.0001) vs. baseline. The area under the cur ve (AUC) during the study period was significantly different for the two is omers (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 dif ferent between responders (S-propranolol 1133.3 +/- 132.0 nmol.h/L; R-propr anolol 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 ther e a correlation between propranolol enantiomer plasma concentrations and th e portal haemodynamic effect. Conclusions: Our data demonstrate a stereoselective metabolism of propranol ol enantiomers in liver cirrhosis. However, following oral propranolol admi nistration, stereoisomer plasma concentrations do not predict the portal ha emodynamic effect.