The Medical Proessorial Unit, St Bartholomew's Hospital, London.
Br J Clin Pharmacol. 1974 Apr;1(2):119-27. doi: 10.1111/j.1365-2125.1974.tb00220.x.
1 The metabolites of thiopurinol have been investigated in intact human and pig erythrocytes using [6-(14)C]-thiopurinol, high voltage electrophoresis and automated cation exchange chromatography. 2 Pre-incubation of human erythrocytes in vitro with thiopurinol increased the formation of hypoxanthine from [8-(14)C]-inosine and simultaneously reduced IMP synthesis. 3 Reduced inosine formation, following one week of thiopurinol therapy, has also been observed in vitro using the intact red cells from three patients suffering from gout. 4 Binding of thiopurinol, and to lesser extents of 6-mercaptopurine, uric acid, oxipurinol and allopurinol, has been demonstrated electrophoretically to human and pig serum proteins. 5 Thiopurinol is shown to have a greater binding capacity for purified human serum albumin than uric acid or 6-mercaptopurine at varying substrate and albumin concentrations covering the physiological range. Under these conditions the binding of uric acid is reduced in the presence of thiopurinol. 6 A comparison of the distribution of thiopurinol, 6-mercaptopurine, allopurinol and oxipurinol in whole blood has revealed that allopurinol and oxipurinol are not irreversibly bound to cellular proteins; whereas 30% and 13% of the total cellular uptake was irreversibly bound in the case of thiopurinol and 6-mercaptopurine respectively at substrate levels of 1 nmol per μl blood.
使用[6-(14)C]-硫唑嘌呤、高压电泳和自动化阳离子交换色谱法，研究了硫唑嘌呤在完整的人和猪红细胞中的代谢产物。
体外预先孵育人红细胞会增加[8-(14)C]-肌苷转化为次黄嘌呤的形成，同时减少 IMP 合成。
在体外使用来自三名痛风患者的完整红细胞也观察到，在一周的硫唑嘌呤治疗后，次黄嘌呤的形成减少。
已通过电泳证明，硫唑嘌呤（以及较小程度的 6-巯基嘌呤、尿酸、氧嘌呤醇和别嘌醇）与人血清和猪血清蛋白结合。
与尿酸或 6-巯基嘌呤相比，硫唑嘌呤在不同的底物和白蛋白浓度下，对纯化的人血清白蛋白具有更大的结合能力，涵盖了生理范围。在这些条件下，在存在硫唑嘌呤的情况下，尿酸的结合减少。
对全血中硫唑嘌呤、6-巯基嘌呤、别嘌醇和氧嘌呤醇的分布进行比较，发现别嘌醇和氧嘌呤醇未与细胞蛋白不可逆结合；而在底物水平为 1 nmol/μl 血液时，硫唑嘌呤和 6-巯基嘌呤的总细胞摄取量的 30%和 13%分别不可逆地结合。
