血卟啉单甲醚在荷瘤小鼠体内的分布

Distribution of Hematoporphyrin Monomethyl Ether in Tumor-bearing Mice

血卟啉单甲醚(代号PsD-044)是一种新的肿瘤光化学诊治剂。本文报道用荧光分光光度法测定PsD-044在S_(180)肉瘤荷瘤小鼠体内的分布及肿瘤与不同组织问的分布比。静注20 mg/kg的PsD-044 30 min后,不同组织中的药物浓度均达峰值。药后3 h,药物在肿瘤与皮肤及骨骼肌间的分布差距最大,肿瘤/皮肤和肿瘤/骨骼肌分布比分别为3和12.2。此时,各组织中的药物浓度依次为肝>肿瘤>肺>皮肤>肾>脾≈心肌≈骨骼肌。药物从组织中消除较快。实验结果表明,PsD-044未能透过血-脑屏障而进入脑组织。在小鼠体内的药物动力学符合三房室模型,所测的主要药物动力学参数与组织分布测定结果基本一致。

Hematoporphyrin monomethyl ether (PsD-044) is a new promising tumor-photolocalizing and photochemotherapeutic agent, and its distribution in different tissues of S180 sarcoma-bearing mice was determined by fluorspectrophotonietry. The peak values of drug concentration in diffrent tissues ap- peared at 30 min after i.v. administration of 20 mg/kg of PsD-044. The maximum values of tumor to muscle and tumor to skin ratios were 12. 2 and 3 respectively, which was achieved at 3 h post drug injection. Drug concentrations in different tissues at this time were in order of liver>tumor>lung>skin> kidney>spleen(?)heart(?)muscle.The pharmacokinetics of PsD-044 in mice was fitted by an open three compartment model. The pharmacokinetic parameters calculated were shown to be essentially consistent with the determination of tissue distribution. It was also shown that PsD-044 can't pass through blood-brain barrier.