Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Marii Magdaleny 14, PL 61-861 Poznań, Poland.
Pharmacol Rep. 2011;63(6):1518-25. doi: 10.1016/s1734-1140(11)70715-0.
Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect drug absorption and pharmacokinetic parameters (PK). The need to apply orally administered analgesics in this group of patients is often related with alternative application of currently available generic products. Thus, from the clinical point of view it is necessary to evaluate the PK of these drugs to confirm their equivalence. The aim of the study was therefore an analysis of the pharmacokinetics of paracetamol from two generic products in patients after total gastric resection. The research was carried out on two groups of patients after gastrectomy with Roux-en-Y reconstruction (n = 30; mean [SD] age, 63.0 [11.5] years; weight, 67.6 [13.7] kg; and height, 166.4 [9.1] cm). The patients received paracetamol in a single orally administered dose of 1,000 mg. Blood samples were collected within 6 h of drug administration. The concentration of paracetamol and paracetamol glucuronide in the blood plasma was marked by means of a validated high-pressure liquid chromatography with ultraviolet detection (HPLC-UV). The main PK for paracetamol in group 1 (n = 17) and 2 (n = 13) were as follows: C(max), 9.46 (3.66) and 12.79 (5.32) μg/ml, respectively (p = 0.0517); AUMC(0-t), 77.64 (30.37) and 51.01 (15.76) μg h(2)/ml (p = 0.0046); AUC(0-inf), 41.61 (23.52) and 30.28 (9.74) μg h/ml (p = 0.0862); t(max), 1.68 (0.63) and 0.50 (0.25) h (p < 0001). The obtained C(max) and AUC values in patients after gastrectomy were reduced in comparison with healthy subjects. Total gastrectomy therefore affected the pharmacokinetics of paracetamol administered in tablets. In our patients, we also observed significant differences between the PK of paracetamol and two generic preparations. These two drugs can thus be used interchangeably, but with caution.
胃切除术会导致消化道发生病理生理变化，这可能会影响药物吸收和药代动力学参数（PK）。这群患者通常需要使用口服止痛药，而这又常常涉及到目前可获得的通用产品的替代应用。因此，从临床角度来看，有必要评估这些药物的 PK，以确认其等效性。因此，本研究的目的是分析全胃切除术后两种通用产品的扑热息痛的药代动力学。该研究在两组接受 Roux-en-Y 重建的胃切除术后患者（n=30；平均[标准差]年龄 63.0[11.5]岁；体重 67.6[13.7]kg；身高 166.4[9.1]cm）中进行。患者接受单次口服 1000mg 扑热息痛。在给药后 6 小时内采集血样。采用经验证的高效液相色谱法（HPLC-UV）结合紫外检测法（UV）检测血浆中扑热息痛和扑热息痛葡萄糖醛酸的浓度。第 1 组（n=17）和第 2 组（n=13）的扑热息痛主要 PK 参数如下：C(max)分别为 9.46（3.66）和 12.79（5.32）μg/ml（p=0.0517）；AUMC(0-t)分别为 77.64（30.37）和 51.01（15.76）μg·h2/ml（p=0.0046）；AUC(0-inf)分别为 41.61（23.52）和 30.28（9.74）μg·h/ml（p=0.0862）；t(max)分别为 1.68（0.63）和 0.50（0.25）h（p<0.001）。与健康受试者相比，胃切除术后患者的 C(max)和 AUC 值降低。因此，全胃切除术影响了片剂形式给予的扑热息痛的药代动力学。在我们的患者中，我们还观察到扑热息痛与两种通用制剂的 PK 之间存在显著差异。因此，这两种药物可以互换使用，但需谨慎。
