间断和连续给药方式对哌拉西林在组织和血浆分布的动力学研究

The pharmacokinetic model of piperacillin concentrations in plasma and tissue by intermission and continuous infusion

目的:通过间断和连续输注2种给药模式使用哌拉西林,观察哌拉西林血浆和皮下组织浓度的药动学模型,并对2种方式的药效学治疗结果进行评估。方法:对14例确诊的或疑似败血症重症患者进行了研究,将患者随机分成接受哌拉西林间断给药组(7例)和连续输注组(7例)。在治疗开始后的第1天和第2天测定血浆和组织中的药物浓度并建立独立的药动学模型。结果:哌拉西林用量连续输注组比间断给药组少25%,在第1天间断给药组的血浆浓度较高(8.7 mg.L-1对5.2 mg.L-1;P=0.08)。但在第2天时连续输注组的中位血浆浓度显著较高(17.9 mg.L-1对5.1 mg.L-1;P<0.005)。2组的中位组织浓度在第1天(连续输注组3.1 mg.L-1对间断组2.6 mg.L-1;P=0.37)无明显差别,在第2天(输注组6.4 mg.L-1对间断组1.2 mg.L-1;P=0.02)有显著差异性。双室药动学模型能够很好地描述得到的数据。利用连续输注给药较成功地获得了组织药效学指标。结论:与标准的间断给药相比,连续输注使用的哌拉西林的量可减少25%,但能够维持较高的波谷浓度。在输入后的第2天输注组组织浓度和血浆浓度明显高于间断治疗组。这说明连续输注治疗比间断给药治疗时哌拉西林的组织渗透性更好,更有利于严重败血症的治疗。

OBJECTIVE To observe piperacillin concentrations in plasma and subcutaneous and treatment outcome tissue when administered by intermission and continuous infusion in critically ill patients.METHODS 14 critically ill adult patients with known or suspected sepsis were conveniently sampled.Patients were randomized to receive different daily doses of piperacillin-tazobactam by intermission or continuous infusion（continuous 7 patients;intermission 7 patients）.Separate pharmacokinetic models were developed for both intermission and continuous dosing.RESULTS The continuous infusion group was administered with a 25% lower piperacillin dose W The median plasma concentrations is higher on day l in the intermission dosing group（8.7 mg·L-1 vs.5.2 mg·L-1;P=0.08）.But the infusion group had statistically significantly higher median plasma concentrations than the intermission group on day 2（17.9 mg·L-1 vs.5.1 mg·L-1;P0.005）.Median tissue concentrations were not statistically different on day l（infusion group 3.1 mg·L-1 vs.intermission group 2.6 mg·L-1;P=0.37）.But in the day 2 Median tissue concentrations were statistically different（infusion group 6.4 mg·L-1 vs.intermission group 1.2 mg·L-1;P=0.02）.A two-compartment pharmacokinetic model was found to describe the data best.Tissue pharmacodynamic targets were achieved more successfully with infusion dosing.CONCLUSION A 25% lower dose of piperacillin administered by continuous infusion seems to maintain higher trough concentrations compared with standard bolus dosing.It is benefit to patients with sepsis.