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目的考察注射用多尼培南在中国健康人体单次给药的临床药代动力学特性,为临床推荐优化的治疗方案。方法 12例健康志愿者按拉丁方三交叉试验设计,随机先后单剂量静脉滴注多尼培南0.25、0.5、1.0g,采用高效液相色谱法分离紫外检测法(HPLC-UV)测定人血浆及尿中多尼培南浓度。用Phoenix○R WinNonlin○R6.1药代动力学程序计算得到非房室模型统计矩参数,并进行药代动力学特征分析。结果单次静脉滴注多尼培南0.25、0.5、1.0g后,血药峰浓度(Cmax)分别为(11.81±1.52)、(22.80±3.80)和(47.26±8.38)μg/mL;达峰时间(Tmax)分别为(60.42±1.44)、(58.33±5.77)和(60.00±0)min;半衰期(t1/2)分别为(63.48±10.51)、(69.12±16.72)和(69.30±11.71)min;药时曲线下面积(AUC0~t)分别为(1 100.86±150.04)、(2 111.50±359.58)和(4 359.50±789.38)μg/(mL·min)。直线回归分析和置信区间法分析均提示本品具有线性药代动力学特征。本品主要经肾脏排泄,给药后24h尿液累积排泄率为70%~75%。本品安全性较好,不良反应发生率为19.44%,均为轻度。结论注射用多尼培南具有线性动力学特征,男女患者应用本品无需调整给药剂量。
Objective To investigate the clinical pharmacokinetics of doxepin for injection in healthy single-dose human in China, and to provide an optimal treatment plan for clinical practice. Methods Twelve healthy volunteers were enrolled in a three-crossover trial of Latin square. Randomized single-dose intravenous injection of doxepin 0.25, 0.5, and 1.0 g was performed. HPLC-UV was used to determine the plasma levels of human plasma And the concentration of dornipamide in the urine. The statistical moment parameters of the non-atrioventricular model were calculated using the Phoenix ○ R WinNonlin ○ R6.1 pharmacokinetic program and the pharmacokinetic characteristics were analyzed. Results After a single intravenous injection of 0.25, 0.5 and 1.0 g of doxepin, the peak plasma concentrations (Cmax) were (11.81 ± 1.52), (22.80 ± 3.80) and (47.26 ± 8.38) μg / mL, respectively (Tmax) were (60.42 ± 1.44), (58.33 ± 5.77) and (60.00 ± 0) min, respectively. The half life (t1 / 2) were 63.48 ± 10.51, 69.12 ± 16.72 and 69.30 ± 11.71, min. The area under the curve (AUC0 ~ t) was (1 100.86 ± 150.04), (2 111.50 ± 359.58) and (4 359.50 ± 789.38) μg / (mL · min), respectively. Linear regression analysis and confidence interval analysis showed that the product has linear pharmacokinetic characteristics. This product is mainly excreted by the kidneys, 24 hours after administration of urine cumulative excretion rate of 70% to 75%. This product is safe, the incidence of adverse reactions was 19.44%, all mild. Conclusion Donepenem for injection has a linear kinetic characteristics, the male and female patients need to adjust the dose of this product.