单剂注射用盐酸多西环素的药动学研究

Single dose pharmacokinetics of doxycycline hydrochloride for injection

目的研究健康成年志愿者单剂静脉滴注盐酸多西环素的药动学。方法按GCP指导原则设计试验方案,选择9名健康受试者分别依次单剂静脉滴注100、200、300mg三个剂量的注射用盐酸多西环素,用HPLC测定血药浓度,采用3P87软件进行数据处理,求出药动学参数。结果受试者分别给药后,药-时曲线符合二房室模型,主要药动学参数cmax分别为(3.02±1.17)、(3.85±1.51)和(10.17±2.81)mg/L;t1/2β分别为(24.09±2.77)h、(21.03±8.25)h、(22.77±5.04)h;AUC0～∞分别为(29.53±10.67)、(37.18±12.60)和(125.43±67.15)mg·h/L。72h尿药累积排泄率分别为(41.44±9.77)%、(46.09±7.05)%、(40.74±3.98)%,说明肾不是主要排泄器官,对肾功能不全者无明显体内蓄积。结论9名健康受试者分别静脉滴注盐酸多西环素,药-时曲线符合二房室模型,在100～300mg剂量范围内药物体内过程呈线性动力学特征。

Objective To investigate the pharmaeokineties of single dose doxycycline hydrochloride for injection by intravenous drip infusion. Methods The protocol was designed according to GCP principle. Nine volunteers who administered intravenously 100, 200 and 300mg doxyeyeline hydroehloride respectively, and the drug concentrations in serum were determined by HPLC method. The pharmaeokineties parameters were calculated by 3P87 software. Results The serum concentration-time eurve fit two eompartment model after intravenous administration of doxyeyeline hydroehloride for injection of 100, 200 and 300mg. The main pharmaeokinetie parameters： cmax, were （3.02 ± 1.17）, （3.85 ± 1.51） and （10. 17 ±2.81） mg/L in three doses respectively; t1/2β were （24.09 ±2.77） h, （21.03±8.25） h and （22.77±5.04）h respectively; AUC0-∞ were （29.53±10.67）, （37.18±12.60） and （125.43±67.15）mg · h/L respectively. The cumulative reeovery in urine in 72h were （41.44±9.77）% , （46.09 ±7.05）% and （40.74 ±3.98）% respectively. The results suggested that the kidney is not the main emunetory and there were no obvious accumulation effects to renal inadequacy patients. Conclusion The serum concentration-time curve of doxyeyeline hydroehloride fit two-compartment model. The pharmaceutical characteristics of doxyeycline hydroehloride in human body were linear in the range of 100mg - 300mg.