Schaefer H G, Harrison D, Hocking M P, Limberg J, Derendorf H
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610.
J Pharm Sci. 1990 Apr;79(4):292-4. doi: 10.1002/jps.2600790404.
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.
研究了部分胃切除对6只犬体内(+)-和(-)-普萘洛尔药代动力学参数的影响。手术前后口服(±)-普萘洛尔(3mg/kg体重),采用间接对映体分离技术测定血浆中(+)-和(-)-普萘洛尔的浓度。(+)-和(-)-普萘洛尔的浓度-时间曲线下面积(AUC)和最大血浆浓度(Cmax)存在显著差异(p≤0.05,配对t检验)。AUC(+):AUC(-)的比值为1.73±0.28。术后对映体之间的这些差异保持不变。其他药代动力学参数无立体选择性。部分胃切除术后,两种对映体达到最大血浆浓度的时间(tmax)和吸收半衰期略有下降,但无统计学意义。最大血浆浓度略有升高。手术前后消除半衰期和平均驻留时间保持不变。因此,部分胃切除术后(+)-和(-)-普萘洛尔的药代动力学不太可能出现任何具有临床意义的变化。