Effects of Truncal Vagotomy and Partial Gastrectomy on the Pharmacokinetics of Propranolol Enantiomers in Dogs

Abstract

The effect of partial gastrectomy on the pharmacokinetic parameters of (+)- and (–)-propranolol were investigated in six dogs. (±)-Propranolol (3 mg/kg body weight) was administered orally before and after surgery and the plasma concentrations of (+)- and (–)-propranolol were determined using an indirect enantioseparation technique. There were significant differences (p ≦ 0.05, paired t-test) in the area under the concentration–time curves (AUCs) and the maximum plasma concentration (Cmax) between (+)- and (–)-propranolol. The ratio AUC(+):AUC(–) was 1.73 ± 0.28. These differences between the enantiomers remained unchanged after surgery. Other pharmacokinetic parameters showed no stereoselectivity. After partial gastrectomy, there was a slight, but nonsignificant decrease in time to reach maximum plasma concentration (tmax) and in the absorption half-life for both enantiomers. The maximum plasma concentration increased slightly. The elimination half-life and the mean residence time remained unchanged before and after surgery. Therefore, it is unlikely that there are any clinically relevant changes in the pharmacokinetics of (+)- and (–)-propranolol after partial gastrectomy.