注射用阿莫西林钠克拉维酸钾(10∶1)临床药代动力学研究

Pharmacokinetics Study of Amoxicillin Sodium Clavulanate Potassium(10∶1) Injection in Healthy Volunteers

目的研究健康受试者接受单次和多次给予注射用阿莫西林钠克拉维酸钾(10∶1)后的药代动力学特征,以指导制定合理的临床给药方案。方法采用输液泵恒速静滴30min给药,分别于给药前和开始给药后10、20、30、45min和1、1.25、1.5、2、2.5、3、4、6、8、10h采集静脉血4mL。采用液相色谱-质谱/质谱法测定人血浆中阿莫西林和克拉维酸浓度,经DAS 2.0.1软件药代动力学程序处理,得主要药代动力学参数。结果阿莫西林和克拉维酸的体内过程均符合权重系数为1/cc的三室模型或二室模型。为避免房室模型拟合所致偏倚,本研究采用非房室模型统计矩参数,单次静滴注射用阿莫西林钠克拉维酸钾(10∶1)0.55、1.1、2.2g后,峰浓度、药时曲线下面积、消除半衰期和清除率等药代参数提示阿莫西林和克拉维酸均具有线性动力学特征。受试者接受单次和多次给药后,阿莫西林和克拉维酸的药代动力学参数接近,且第7～13次给药前的谷浓度均低于最低检测限,表明每次给药前,前一次给药已基本清除,多次给药后无蓄积。结论注射用阿莫西林钠克拉维酸钾(10∶1)具有线性动力学特征,1.1g,Q8h给药能满足临床治疗需要。

Objective To study the pharmacokinetics of amoxicillin sodium clavulanate potassium （10 ： 1） injection with different single doses intravenous infusion and one dose repeated intravenous injection in healthy volunteers for guiding the rational clinical regimen. Methods Using infusion pump constantly intravenous dripping in 30 rain, 4 mL blood samples were collected before and after the administration at 10 rain, 20 min, 30 rain, 45 min, and 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10 h. The plasma concentrations of amoxicillin and clavulanate were detected by high performance liquid chromatography- mass spectrometry/mass spectrometry method. The pharmacokinetic parameters were calculated by DAS2.0.1 software. Results The dispositions of amoxicillin and clavulanate matched three or two compartment model with the weight coefficient 1/cc. To avoid the biases caused by compartment model fitting, the pharmacokinetic parameters were statistical moment parameters of non-compartment model. The peak concentrations, the areas under curve, the half-lifes and the clearances after single injections of 0.55 g, 1.1 g and 2.2 g indicated that both amoxillin and clavulanate had linear dynamics characteristics. After 1.1 g single dose and multiple doses infusion, the pharmacokinetic parameters of amoxicillin and clavulanate were close respectively, and the trough concentrations before the 7th to 13th administration were lower than the detection limitation, which implied that the previous administration had cleared out before the next administration, and no accumulation happened after multiple doses. Conclusions The amoxicillin sodium clavulanate potassium （10 ： 1） injection possesses the linear kinetics. The dosage regimen of 1.1 g Q8h intravenous infusion could meet the needs of clinical therapy.