光敏剂m-THPC在原位移植性肝癌大鼠体内的组织分布和药代动力学研究

目的 探讨光敏剂m-THPC在原位移植性肝癌大鼠体内的分布和消除情况,为m-THPC光动力治疗肝癌提供参考和依据.方法 大鼠尾静脉注射m-THPC 0.3 mg/kg后,采用荧光分光光度计法测定组织和血浆中的原形药物浓度,用PK-GRAPH程序拟合并计算药代动力学参数.结果 m-THPC血药浓度-时间曲线符合二室模型,血浆分布半衰期(T1/2α)为1.18 h,血浆消除半衰期(T1/2β)为22.57 h.药物在大鼠体内分布广泛,各组织药物浓度均在40 ng/g以上;其中肝脏组织浓度最高,肝癌次之,肌肉、皮肤组织相对较低,给药6 h后多数组织药物浓度达到最高,24 h后多数组织药物浓度有所下降,而肝癌药物浓度在24 h达到最高,肝癌和正常组织药物分配比也达到最高.结论 m-THPC在大鼠组织中分布广泛,血浆药物清除相对较快;给药后24 h是肝癌光动力治疗的最佳时间窗.

Abstract：

Objective To study the pharmacokinetics, distribution and excretion of m-THPC in rat models of liver cancer via orthotropic implantation using Walker-256. Methods After an intravenous injection of m-THPC with 0.3 mg/kg, the concentrations of m-THPC in biological specimens were determined by a fluorescence method. The data obtained were processed with PK-GRAPH pharmacokinetic procedure. Results The disposion of m-THPC in rat models of liver cancer Walker-256 was conformed to a two compartment model with T1/2α = 1.18 h, T1/2β =22. 57 h at the dose of 0. 3 mg/kg. m-THPC was shown to be widely distributed to the various tissues. There was a highest drug accumulation in liver and liver cancer, and lowest in skin and muscle. Ratio of m-THPC concentration in the Walker-256 tumor compared to normal tissue reach the peak 24 h after m-THPC administration. Conclusions m-THPC is distributed widely and eliminated at a rapid rate in Walker-256 rats. Twentyfour hours after m-THPC administration may be the best time for photodynamic therapy of liver cancer.

Pharmacokinetics of photosensitizer m-THPC in rat models of liver cancer via orthotropic implantation using walker-256

Objective To study the pharmacokinetics, distribution and excretion of m-THPC in rat models of liver cancer via orthotropic implantation using Walker-256. Methods After an intravenous injection of m-THPC with 0.3 mg/kg, the concentrations of m-THPC in biological specimens were determined by a fluorescence method. The data obtained were processed with PK-GRAPH pharmacokinetic procedure. Results The disposion of m-THPC in rat models of liver cancer Walker-256 was conformed to a two compartment model with T1/2α = 1.18 h, T1/2β =22. 57 h at the dose of 0. 3 mg/kg. m-THPC was shown to be widely distributed to the various tissues. There was a highest drug accumulation in liver and liver cancer, and lowest in skin and muscle. Ratio of m-THPC concentration in the Walker-256 tumor compared to normal tissue reach the peak 24 h after m-THPC administration. Conclusions m-THPC is distributed widely and eliminated at a rapid rate in Walker-256 rats. Twentyfour hours after m-THPC administration may be the best time for photodynamic therapy of liver cancer.