Anderson K E, Simionatto C S, Drummond G S, Kappas A
Clin Pharmacol Ther. 1986 May;39(5):510-20. doi: 10.1038/clpt.1986.88.
Tin (Sn4+)-protoporphyrin, a potent competitive inhibitor of heme degradation to bile pigment, was cleared rapidly from plasma in normal subjects (t1/2 approximately 4 hours for plasma levels greater than 5 nmol/ml, with evidence of dose-dependent pharmacokinetics at lower plasma concentrations). Small amounts were excreted promptly in urine (0.1% to 5.6%) and more gradually in feces (3.7% to 11.3%). The only dose-limiting (greater than 1.0 mumol/kg, single dose) side effect was mild sensitivity to sunlight and long-wave ultraviolet light. Absorption after intramuscular administration was rapid, but there was no absorption after oral dosing. In bile duct-ligated rats treated with Sn-protoporphyrin, there was a substantial (approximately 50%) reduction in plasma bilirubin levels compared with levels in ligated control animals. Seven studies were carried out in four women with moderate to severe cholestasis secondary to primary biliary cirrhosis and in two men with Gilbert's syndrome. In these studies Sn-protoporphyrin (total doses of 0.25 to 2.0 mumol/kg body weight) reduced plasma bilirubin levels to a varying degree (7% to 43%) promptly after its intravenous administration.
锡（Sn4+）-原卟啉是血红素降解为胆色素的一种强效竞争性抑制剂，在正常受试者体内可迅速从血浆中清除（血浆浓度大于5 nmol/ml时，t1/2约为4小时，在较低血浆浓度下有剂量依赖性药代动力学证据）。少量药物迅速经尿液排泄（0.1%至5.6%），经粪便排泄则较为缓慢（3.7%至11.3%）。唯一的剂量限制性（单剂量大于1.0 μmol/kg）副作用是对阳光和长波紫外线轻度敏感。肌内注射后吸收迅速，但口服给药后无吸收。在用锡原卟啉治疗的胆管结扎大鼠中，与结扎对照动物相比，血浆胆红素水平大幅降低（约50%）。对4名原发性胆汁性肝硬化继发中度至重度胆汁淤积的女性和2名患有吉尔伯特综合征的男性进行了7项研究。在这些研究中，锡原卟啉（总剂量为0.25至2.0 μmol/kg体重）静脉给药后可迅速使血浆胆红素水平不同程度降低（7%至43%）。
