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

Pharmacokinetics of photosensitizer m-THPC in rat models of liver cancer via orthotropicimplantation using Walker-256

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-THPC0．3mg／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1．18h，血浆消除半衰期（T1/2p）为22．57h。药物在大鼠体内分布广泛，各组织药物浓度均在40ng／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6h后多数组织药物浓度达到最高，24h后多数组织药物浓度有所下降，而肝癌药物浓度在24h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24h是肝癌光动力治疗的最佳时间窗。

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 Tl/2Cx = 1. 18 h, TI/213 =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.