胃部分切除术后患者中普萘洛尔和阿替洛尔的药代动力学：一项对比研究。

Wójcicki J, Wojciechowski G, Wójcicki M, Kostyrka R, Sterna R, Gawronska-Szklarz B, Pawlik A, Drozdzik M, Kozlowski K

Department of Experimental and Clinical Pharmacology, Pomeranian University School of Medicine, Szczecin, Poland.

Eur J Clin Pharmacol. 2000 Apr;56(1):75-9. doi: 10.1007/s002280050724.

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.

CONCLUSION

Partial gastrectomy with B1 anastomosis affects the pharmacokinetics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).

目的

部分胃切除术会改变胃肠道的解剖结构和分泌活动。可以预期，这些变化的后果会影响药物动力学，尤其是口服药物的吸收。为了确定普萘洛尔和阿替洛尔在部分胃切除术后患者中的药代动力学特征，对作为亲脂性和亲水性β肾上腺素能受体拮抗剂代表的这两种药物进行了研究。

方法

该研究对29例行毕罗Ⅰ式（B1）吻合术的胃切除术后患者以及18名健康志愿者作为对照进行。分别单次口服80 mg普萘洛尔和100 mg阿替洛尔后，按照交叉方案研究其药代动力学。给药后24小时内采集10次血样。使用具有一级吸收的单室开放模型计算普萘洛尔和阿替洛尔的药代动力学参数。

结果

胃切除患者中普萘洛尔的平均血浆浓度低于对照组，在观察期的1.5小时至6.0小时之间达到显著差异。接受手术的受试者中普萘洛尔的药代动力学参数与健康人不同。我们观察到浓度-时间曲线下面积显著降低（32%），血浆峰浓度降低（20%），半衰期增加（25%）。部分胃切除术后患者中阿替洛尔的平均血浆浓度和药代动力学参数与对照组无显著差异。未发现部分胃切除术后的时间间隔与所研究药物的药代动力学参数之间存在关联。