健康人体静脉滴注头孢西酮钠的药动学研究

Pharmacokinetic Study of Cefazedone Sodium Given by Intravenous Drip Infusion in Healthy Volunteers

目的研究单次及多次静脉滴注头孢西酮钠在中国健康志愿者体内的药动学特征。方法 30名健康受试者(男、女各半)随机分为低、中、高3个剂量组,分别单次静脉滴注头孢西酮钠0.5、1.0、2.0 g,中剂量组继续给药,按每天给药2次,每次1.0 g,连续给药5 d,用LC-MS/MS测定受试者不同时间点血浆中药物浓度,经DAS 2.1.1软件计算药动学参数并进行统计分析。结果低、中、高剂量单次给药后头孢西酮钠t1/2z分别为(1.85±0.53)、(1.81±0.29)、(2.07±0.32)h,AUC0-t分别为(145.30±68.67)、(244.26±38.284)、(513.10±127.27)mg.h.L-1,AUC0-∞分别为(147.89±70.45)、(246.60±40.61)、(521.02±134.33)mg.h.L-1,tmax分别为(0.30±0.06)、(0.33±0.00)、(0.35±0.05)h,ρmax分别为(87.18±36.37)、(151.13±19.02)、(271.94±38.86)mg.L-1,Vz分别为(9.97±2.91)、(10.67±1.27)、(11.75±1.78)L,CLz分别为(3.88±1.239)、(4.14±0.57)、(4.03±0.86)L.h-1。多次给药组头孢西酮钠AUCss为(208.93±37.37)mg.h.L-1,AUC0-t为(208.93±37.37)mg.h.L-1,AUC0-∞为(210.64±38.55)mg.h.L-1,tmax为(0.33±0.00)h,ρmax为(130.20±22.83)mg.L-1,平均稳态浓度ρss为(17.41±3.11)mg.L-1,ρmax为(0.89±0.60)mg.L-1,DF为(7.45±0.70),t1/2z为(1.77±0.25)h,Vz为(12.40±2.57)L,CLz为(4.90±0.95)L.h-1。结论健康受试者单次静脉滴注头孢西酮钠0.5、1.0、2.0 g后,其体内药动学过程呈线性动力学特征;性别对头孢西酮钠的体内药动学无差异;多次给药主要药动学参数(tmax、Vz、t1/2z、CLz)与单次给药无显著性差异(P>0.05);连续给药后在体内无蓄积。

OBJECTIVE To investigate the pharmacokinetics of cefazedone sodium in Chinese healthy volunteers after a single or multiple dose of intravenous drip infusion. METHODS Thirty healthy volunteers, half male and half female, were randomly assigned to three groups of single dose and one group of multiple dose. The plasma drug concentrations after intravenous drip of single dose of 0. 5, 1.0, 2. 0 g and multiple dose of 1.0 g cefazedone sodium were determined by HPLC-MS/MS. RESULTS The pbarmacokinetic parameters of cefazedone sodium after single dose of 0. 5, 1.0, 2. 0 g were obtained as follows ： t1/2t were （ 1.85±0. 53 ） , （ 1.81±0. 29）, （2.07±0. 32） h, respectively; AUC0-t were （ 145.30±68.67）, （244. 26± 38. 284）, （513.10±127.27） mg·h·L^-1; AUC0-oo were （147.89±70.45）, （246.60± 40. 61）, （521.02±134.33） mg·h·L^-1; tmax were （0.30±0.06）, （0.33±0.00）, （0.35±0.05） h; ρmax were（87. 18 ±36.37）, （151.13±19.02）,（271.9±±38.86） mg. L-1; V were （9.97±2.91）, （10.67± 1.27）, （ 11.75 ± 1.78） L, CLz were （3.88 ±1. 239）, （4. 14 ±0. 57）, （4. 03 ±0. 86） L·h^-1 , respectively. The muhi-dose phar-maeokinetic parameters of cefazedone sodium were obtained as follows ： AUCss was （ 208, 93 ±37.37） mg·h·L^-1; AUC0-t was （208.93 ±37.37） mg·h·L^-1; AUC0-∞ was （210.64 ±38.55） mg·h·L^-1; t was （0.33±0.00） h; p was（130.20± 22.83）mg·h·L^-1; pss was （17.41 ±3.11） mg·h·L^-1; pmin was （0. 89 ±0. 60） mg·h·L^-1; DF was （7.45 ±0. 70） ; t1/2, was（1.77 ± 0. 25 ） h ; Vz was （ 12.40 ± 2. 57 ） L ; CL was （4.90 ± 0. 95 ） mg·h·L^-11. CONCLUSION Cefazedone sodimn displays linear pharmaeo- kinetics in the dose range of 0. 5 to 2 g after single intravenous drip injection. No significant differences between genders are observed. The differences of the main pharmaeokinetie parameters of t t1/2, Vz and CLz between each group are not significant（ P 〉 0. 05 ）. There is no significant accumulation of eefazedone sodium in healthy volunteers after multiple intravenous drip injection. KEY WORDS：eefazedone; LC-MS/MS; pharmacokinetics