摘要
目的研究国产洛铂在恶性肿瘤患者体内的药动学特点,为该药的合理应用奠定理论依据。方法将洛铂按照50 mg.m-2体表面积给8例恶性肿瘤患者输注后,采集不同时间静脉血及其手术中切取恶性肿瘤组织,应用高效液相色谱方法,检测8例恶性肿瘤患者血浆、恶性肿瘤组织中的药物浓度。结果患者输注洛铂后0,0.2,0.5,1,2,4,6,8,12,24 h,检测外周血中洛铂的平均药物浓度分别为(2.626±0.31)×104,(1.683±0.2)×104,(1.124±0.163)×104,(6.43±1.45)×103,(4.45±1.57)×103,(2.19±0.26)×103,(1.53±0.25)×103,(0.79±0.18)×103,(0.47±0.11)×103,(0.02±0.01)×103μg.L-1;洛铂在恶性肿瘤病人血浆中药动学符合二室模型拟合,各药动学参数分别为:最大血药浓度(ρmax)为(2.626±0.31)×104μg.L-1;分布半衰期(t1/2α)为(15±2.4)min;消除半衰期(t1/2β)为(162±15)min;药物由周边室至中央室的转运速率常数(k21)为(1.00±0.28)h-1;药物自中央室消除速率常数(k10)为(0.74±0.11)h-1;药物自中央室至周边室的转运速率常数(k12)为(1.31±0.27)h-1;药-时曲线下面积(AUC)(35.20±5.47)μg.h.L-1;血浆清除率(CL)(8.73±1.51)L.h-1。8例患者肿瘤组织手术标本中,肺和乳腺癌肿瘤组织中,洛铂的平均血药浓度分别为(0.33±0.12),(0.23±0.15)mg.L-1,明显高于输注24 h后血浆中的洛铂浓度(0.02±0.01)mg.L-1(P<0.01)。结论按照50 mg.m-2体表面积给药后,在肿瘤患者血浆中洛铂药动学符合二室模型拟合,优于文献报道的国外同类产品。
OBJECTIVE To study the pharmacokinetics of lobaplatin in patients with malignant.METHODS 8 Patients(35 to 56y) received a single dose of lobaplatin 50 mg·m^-2 intravenously for 2 h.Plasma was obtained after the infusion for the determination of lobaplatin concentrations.Lobaplatin concentrations were measured using high-performance liquid chromatograpy(HPLC).The pharmacokinetic parameters were calculated by using PKS software.RESULTS The mean concentrations of lobaplatin at 0,0.2,0.5,1,2,4,6,8,12 and 24 h after infusion were(2.626±0.31)×10^4,(1.683±0.2)×10^4,(1.124±0.163)×10^4,(6.43±1.45)×10^3,(4.45±1.57) ×10^3,(2.19±0.26)×10^3,(1.53±0.25) ×10^3,(0.79±0.18) ×10^3,(0.47±0.11) ×10^3 and(0.02±0.01) ×10^3μg·L^-1 respectively.The pharmacokinetic parameters were as follows:ρmax(2.626±0.31)×10^4μg·L^-1,t1/2α(0.25±0.04)h,t1/2β(2.70±0.25)h,k21(1.00±0.28)h^-1, k10(0.74±0.11)h^-1,k12(1.31±0.27)h^-1,AUC(35.20±5.47)μg·h·L^-1,CL(8.73±1.51)L·h^-1.CONCLUSION Pharmacokinetics of lobaplatin follows biphasic kinetic models.The pharmacokinetic parameters of lobaplatin and its metabolite are higher than those reported.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2007年第24期1888-1891,共4页
Chinese Pharmaceutical Journal
基金
河北省科技厅科技攻关项目(05276101D-59)