Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary.
Kalász Teaching and Research Co., Gvadányi utca 44-46, 1144 Budapest, Hungary.
Molecules. 2020 Mar 10;25(5):1250. doi: 10.3390/molecules25051250.
Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, kidneys, liver, lung, eyes, and testes tissues were taken after 5, 15, 30, 60, and 120 min and analyzed using reversed-phase high-performance liquid chromatography. K-203, K-867, or K-870 was present in every tissue that was analyzed, including the serum, the eyes, testes, liver, kidneys, lungs, and the brain. The serum levels of K-867 and K-870 (chlorine-substituted derivatives of K-203) were nearly constant between 15 and 30 min, while their parent compound (K-203) showed peak level at 15 min after the administration of 30 µmol/rat. Neither K-203, nor K-867 or K-870 were toxic at a dose of 100 µmol/200 g in rats. Chlorine-substitution of K-867 and K-870 produced limited absorbance and distribution compared to their parent compound, K203.
我们的目的是寻找氯取代的抗有机磷中毒解毒剂，并将其药代动力学与母体化合物 K-203 进行比较。雄性 Wistar 大鼠肌肉注射 K-203、K-867 或 K-870。在 5、15、30、60 和 120 分钟后采集血清、脑、肾、肝、肺、眼和睾丸组织，并使用反相高效液相色谱法进行分析。K-203、K-867 或 K-870 存在于分析的每一种组织中，包括血清、眼睛、睾丸、肝脏、肾脏、肺和大脑。K-867 和 K-870（K-203 的氯取代衍生物）的血清水平在 15 至 30 分钟之间几乎保持不变，而其母体化合物（K-203）在 30µmol/rat 给药后 15 分钟达到峰值水平。在大鼠中，即使剂量为 100µmol/200g，K-203、K-867 或 K-870 也没有毒性。与母体化合物 K203 相比，K-867 和 K-870 的氯取代物的吸收和分布有限。
