国产注射用洛铂在恶性肿瘤患者体内药动学的研究

 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(ρ_max)为(2.626±0.31)×104μg·L^-1;分布半衰期(t_1/2α)为(15±2.4)min;消除半衰期(t_1/2β)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。}

Study on Lobaplatin Pharmacokinetic in Human Plasma and Tumor Tissue of Malignant Patients

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)×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 and(0.02±0.01) ×10³μg·L^-1 respectively.The pharmacokinetic parameters were as follows:ρ_max(2.626±0.31)×104μg·L^-1,t_1/2α(0.25±0.04)h,t_1/2β(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.