Pharmacokinetics of propranolol and atenolol in patients after partial gastric resection: a comparative study

Objective: Partial gastric resection alters the anatomy and secretory activ ity of the gastrointestinal tract. It might be expected that the consequenc es of such changes should affect the pharmacokinetics, especially concernin g the absorption of orally administered drugs. Propranolol and atenolol, as representatives of lipophilic and hydrophilic beta-adrenoreceptor antagoni sts, have been studied in order to define their pharmacokinetic characteris tics in patients after partial gastrectomy. Methods: The study was carried out in 29 patients after gastric resection w ith Billroth I (B1) anastomosis and in 18 healthy volunteers as controls. P harmacokinetics of propranolol and atenolol was investigated after a single oral dose of 80 mg and 100 mg, respectively, following a cross-over schedu le. Blood samples were collected ten times during the 24 h after the drug a dministration. 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 gastrect omised patients were lower than those in controls, reaching significance be tween 1.5 h and 6.0 h of the observation period. Pharmacokinetic parameters of propranolol were different in subjects submitted to surgery compared wi th healthy persons. We observed a significant decrease in the area under th e concentration-time curve (32%) and the peak plasma concentration (20%), a nd an increase in half-life (25%). Mean plasma concentrations and pharmacok inetic parameters of atenolol in patients following partial gastric resecti on were not significantly different from those in the controls. No relation ship between time interval following partial gastrectomy and pharmacokineti c parameters of the investigated drugs was noted. Conclusion: Partial gastrectomy with B1 anastomosis affects the pharmacokin etics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).