Effects of truncal vagotomy and partial gastrectomy on the pharmacokinetics of propranolol enantiomers in dogs.
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 less than or equal to 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.
Schaefer
H G
HG
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610.
Harrison
D
D
Hocking
M P
MP
Limberg
J
J
Derendorf
H
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005743:Gastrectomy; D006207:Half-Life; D011433:Propranolol / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D015167:Vagotomy, Truncal
D011433:Propranolol