Upton R A, Ashley J J, Ryan A J
J Pharm Sci. 1978 Mar;67(3):310-4. doi: 10.1002/jps.2600670308.
Blood levels of three aryldihydro-s-triazines in rats were followed: 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-phenyl-s-triazine (I), the prototype of the series; 4,6-diamino-1-(3,4-dichlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine (II); and N-(m-tolyl)-p-(4,6-diamino-1,2-dihydro-2,2-dimethyl-s-triazin-1-yl)hydrocinnamide (III). The blood profiles obtained provide substantial evidence that III, but not II, was precipitated in the peritoneal cavity where it was injected. Precipitation after intraperitoneal injection may explain why III and similar triazines with long nonpolar chains have been reported to be more active against intraperitoneal Walker 256 tumor than is II, even though the latter compound is a far more potent inhibitor of Walker 256 dihydrofolate reductase and of tumor cell cultures in vitro. Precipitation in the peritoneal cavity also may be involved in the difficulty of obtaining the toxicity-free antineoplastic activity expected from certain aryldihydrotriazines selectively inhibiting neoplastic dihydrofolate reductase.
对大鼠体内三种芳基二氢-s-三嗪的血药浓度进行了跟踪监测：该系列的原型4,6-二氨基-1,2-二氢-2,2-二甲基-1-苯基-s-三嗪（I）；4,6-二氨基-1-(3,4-二氯苯基)-1,2-二氢-2,2-二甲基-s-三嗪（II）；以及N-(间甲苯基)-对-(4,6-二氨基-1,2-二氢-2,2-二甲基-s-三嗪-1-基)氢化肉桂酰胺（III）。所获得的血药浓度曲线提供了充分的证据，表明III（而非II）在其注射的腹腔中发生了沉淀。腹腔注射后的沉淀现象或许可以解释，为什么据报道III以及具有长非极性链的类似三嗪对腹腔内的Walker 256肿瘤比II更具活性，尽管后者在体外是Walker 256二氢叶酸还原酶和肿瘤细胞培养物的一种效力强得多的抑制剂。腹腔内的沉淀也可能与难以从某些选择性抑制肿瘤二氢叶酸还原酶的芳基二氢三嗪中获得预期的无毒性抗肿瘤活性有关。
