摘要
目的:研究中国健康志愿者单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后的药动学行为,并评价药动学参数在剂量1.0～4.0g范围内的相关性。方法:12名健康志愿者,随机三交叉试验,分别单剂量静脉滴注注射用头孢替坦二钠1.0,2.0,4.0g;测定给药后24h内的血药浓度和尿药浓度,用DAS Ver 2.0软件计算药动学参数。结果:单剂量静脉滴注1.0,2.0,4.0g注射用头孢替坦二钠后,头孢替坦的消除半衰期大约为3～4h,血浆药物浓度(Cmax)随剂量增加呈线性增加(75.0±10.4～230.7±33.7μg·mL-1)。另外,曲线下面积(AUC)在1.0～4.0g剂量范围内也呈线性增加(AUC0-t:308.5±62.9～1 018.5±164.2μg.h·mL-1,AUC0-∞:314.4±63.2～1 031.7±172.5μg·h·mL-1)。24h尿药累积排泄率分别为65.6%±16.7%、44.4%±10.1%和49.1%±11.2%。结论:在剂量1.0～4.0g范围内头孢替坦呈线性药动学,Cmax、AUC的升高与剂量成正比。除2.0g剂量组t1/2性别间存在显著性差异,其他剂量组tmax、Cmax、t1/2、AUC0-t、CL、Vd、MRT0-t、尿排泄率性别间均无统计学差异。
OBJECTIVE The purposes of the study were to characterize the phammcokinetics of cefotetan single intravenous injec tion doses of 1.0.2. 0.4. 0 g in healthy subjects, and assess the dose proportionality of cefotetan over the potential therapeutic dose range （ 1. 0 - 4. 0 g）. METHODS In a randomized three-way crossover study, twelve healthy subjects was took single intravenous in- jection doses of 1.0,2. 0,4. 0 g cefotetan. Plasma concentrations were determined at selected time intervals for 24 hours. The pharmaco- kinetic paramelers were calculated by DAS software. RESULTS The elimination half-life of cefotetan after i. v 1.0,2. 0,4. 0 g cefotetan was about 3 - 4 h, the peak plasma concentration （Cmax） increased linearly from 75. 0 ± 10. 4 to 230. 7 ± 33. 7 μg-mL^-1 with the in- creasing dose. Moreover, the area under the plasma concentration vs time curve increased linearly within the dose range of 1.0 - 4. 0 g （AUG0-t） from308.5±62.9μg-h.mL·mL^-1 018.5± 164.2μg-h.mL·mL^-1 AUG0-t from314.4±63.2μg-h.mL·mL^-1 to 1031.7± 172. 5μg-h.mL·mL^-1. CONCLUSION Cefotetan exhibits a linear plmrmacokinetic profile at the doses in the range of 1.0 - 4. 0 g. Dose-dependent parameters（Cmax. AUC）increased in an approximately dose proportional manner from 1.0 g to 4. 0 g. Differences in the pharrnacokinetic parameters （tmax, t1/2 .AUG0-t .CL.Vd .MRT0-t、Urinary excretion rate） between genders were not statistically sig- nificant, but difference in t1/2 of 2. 0 g was statistically significant.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第24期1960-1964,共5页
Chinese Journal of Hospital Pharmacy
基金
辽宁省科学技术计划项目(编号:2009412001-4)
