title: Pharmacokinetics of propranolol and atenolol in patients after partial gastric resection: a comparative study.
abstract: OBJECTIVE
  Partial gastric resection alters the anatomy and secretory activity of the gastrointestinal tract. It might be expected that the consequences of such changes should affect the pharmacokinetics, especially concerning the absorption of orally administered drugs. Propranolol and atenolol, as representatives of lipophilic and hydrophilic beta-adrenoreceptor antagonists, have been studied in order to define their pharmacokinetic characteristics in patients after partial gastrectomy.
  
  
  METHODS
  The study was carried out in 29 patients after gastric resection with Billroth I (B1) anastomosis and in 18 healthy volunteers as controls. Pharmacokinetics of propranolol and atenolol was investigated after a single oral dose of 80 mg and 100 mg, respectively, following a cross-over schedule. Blood samples were collected ten times during the 24 h after the drug administration. Pharmacokinetic parameters of propranolol and atenolol were calculated using a one-compartment open model with first-order absorption.
  
  
  RESULTS
  The average blood plasma concentrations of propranolol in gastrectomised patients were lower than those in controls, reaching significance between 1.5 h and 6.0 h of the observation period. Pharmacokinetic parameters of propranolol were different in subjects submitted to surgery compared with healthy persons. We observed a significant decrease in the area under the concentration-time curve (32%) and the peak plasma concentration (20%), and an increase in half-life (25%). Mean plasma concentrations and pharmacokinetic parameters of atenolol in patients following partial gastric resection were not significantly different from those in the controls. No relationship between time interval following partial gastrectomy and pharmacokinetic parameters of the investigated drugs was noted.
  
  
  CONCLUSIONS
  Partial gastrectomy with B1 anastomosis affects the pharmacokinetics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).
authors.affiliation: Department of Experimental and Clinical Pharmacology, Pomeranian University School of Medicine, Szczecin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Wójcicki
authors.forename: G
authors.initials: G
authors.lastname: Wojciechowski
authors.forename: M
authors.initials: M
authors.lastname: Wójcicki
authors.forename: R
authors.initials: R
authors.lastname: Kostyrka
authors.forename: R
authors.initials: R
authors.lastname: Sterna
authors.forename: B
authors.initials: B
authors.lastname: Gawronska-Szklarz
authors.forename: A
authors.initials: A
authors.lastname: Pawlik
authors.forename: M
authors.initials: M
authors.lastname: Drozdzik
authors.forename: K
authors.initials: K
authors.lastname: Kozlowski
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000714:Anastomosis, Surgical; D001262:Atenolol / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D005743:Gastrectomy; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics*; D018709:Statistics, Nonparametric; D013270:Stomach / Q000601:surgery
chemical_list: D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D011433:Propranolol