title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany. schepke@uni-bonn.de
authors.forename: M
authors.initials: M
authors.lastname: Schepke
authors.forename: P
authors.initials: P
authors.lastname: Raab
authors.forename: A
authors.initials: A
authors.lastname: Hoppe
authors.forename: K
authors.initials: K
authors.lastname: Brensing
authors.forename: D
authors.initials: D
authors.lastname: Paar
authors.forename: U
authors.initials: U
authors.lastname: Potyka
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011433:Propranolol