全肾切除术和部分肾切除术对静脉注射扑热息痛在人体药代动力学中的影响。

Karbownik Agnieszka, Polom Wojciech, Porazka Joanna, Szalek Edyta, Grabowski Tomasz, Wolc Anna, Grzesowiak Edmund

Acta Pol Pharm. 2017 May;74(3):929-935.

Paracetamol is one of the most common analgesic and antipyretic drugs. Recently intravenous paracetamol has been widely used to treat moderate postoperative pain. Surgery is the main method of treatment of renal cancer. Total or partial nephrectomy can be performed, depending on the size and location of the tumor. Pharmacokinetics of drugs may depend on the type of surgery. The aim of the study was to compare the postinfusion pharmacokinetics of paracetamol in patients after total nephrectomy (TN) and nephron sparing surgery (NSS).The research was carried out on two groups of patients after nephrectomy: total (TN n = 37; mean [SD], age, 60.4 [10.9] years; BMI, 26.5 [3.8] kg/m2; creatinine clearance, Cl, 80.9 [37.1] mL/min) and nephron sparing surgery (NSS n = 17; 57.9 [16.5] years; BMI, 29.5 [5.3] kg/m2; Cl, 97.6 [27.8] mL/min). The patients were treated with paracetamol (PerfalganO Bristol-Myers Squibb) at an intravenous dose of 1.000 mg, which was infused for 15 minutes after surgery. The concentrations of paracetamol in the patients' plasma were determined by the HPLC method with UV detection (X = 261 run). The main pharmacokinetic parameters of paracetamol in the TN vs. NSS group were as follows: C.. 29.08 [17.39] vs. 27.54 [15.70] pg/mL (p = 0.6692); AUC5, 29.24 [13.86] vs. 34.85 [14.28] pg.h/mL (p = 0.2896); AUMC5,,,, 47.58 [26.08] vs. 62.02 [27.64] pg-h/mL (p = 0.1345); to. 2.34 [0.96] vs. 1.93 [0.50] h (p = 0.1415), respectively. In both groups the exposure to paracetamol was comparable. The t1/2 after nephron sparing surgery was shorter than after total nephrectomy. Therefore, these patients may demand more frequent drug administration. In the NSS group the C. of the analgesic was considerably reduced in men.

对乙酰氨基酚是最常见的止痛和解热药物之一。最近，静脉注射对乙酰氨基酚已被广泛用于治疗中度术后疼痛。手术是治疗肾癌的主要方法。可根据肿瘤的大小和位置进行全肾切除术或部分肾切除术。药物的药代动力学可能取决于手术类型。本研究的目的是比较全肾切除术（TN）和保留肾单位手术（NSS）患者输注对乙酰氨基酚后的药代动力学。

该研究在两组肾切除术后患者中进行

全肾切除术组（TN，n = 37；平均[标准差]，年龄60.4[10.9]岁；体重指数，BMI，26.5[3.8]kg/m²；肌酐清除率，Cl，80.9[37.1]mL/min）和保留肾单位手术组（NSS，n = 17；57.9[16.5]岁；BMI，29.5[5.3]kg/m²；Cl，97.6[27.8]mL/min）。患者接受静脉注射剂量为1000mg的对乙酰氨基酚（必理通®，百时美施贵宝公司）治疗，术后输注15分钟。采用高效液相色谱法（HPLC）和紫外检测（波长λ = 261nm）测定患者血浆中对乙酰氨基酚的浓度。TN组与NSS组对乙酰氨基酚的主要药代动力学参数如下：Cmax，29.08[17.39]对27.54[15.70]μg/mL（p = 0.6692）；AUC0-5，29.24[13.86]对34.85[14.28]μg·h/mL（p = 0.2896）；AUMC0-5，47.58[26.08]对62.02[27.64]μg·h²/mL（p = 0.1345）；t1/2，2.34[0.96]对1.93[0.50]小时（p = 0.1415）。两组患者对乙酰氨基酚的暴露量相当。保留肾单位手术后的t1/2短于全肾切除术后。因此，这些患者可能需要更频繁地给药。在NSS组中，男性患者镇痛剂的Cmax显著降低。