PDF(Pubmed)
Abstract：
KPT-335 (Verdinexor) is a novel SINE that potently inhibits the nucleoprotein Exportin 1 (XPO1/CRM1) of tumor cell lines and reduces the replication level of the influenza virus. KPT-335 is mainly used for the treatment of canine tumors. Drugs for the effective treatment of feline tumors are currently unavailable in China. KPT-335 may have potential in the treatment of cat tumors. However, the effects of KPT-335 in cats are unreported, and no relevant methodology has been established for pharmacokinetic studies. In this study, a UPLC-MS/MS method was developed to determine KPT-335 concentrations in cat plasma, followed by pharmacokinetic studies. Briefly, plasma proteins are precipitated with acetonitrile, and the supernatant was collected for detection after centrifugation. The linearity for KPT-335 in cat plasma was in the range of 5-1,000 ng/mL. Satisfactory accuracy and precision were obtained. The intra-day accuracy was between -4.10% and 10.48%, the precision was ≤4.65%; the inter-day accuracy was between -0.11% and 8.09%, and the precision was ≤5.85%. Intra-day and inter-day accuracy and precision were within regulatory limits. The results of preliminary pharmacokinetic studies were as follows: Tmax was 1.46 ± 0.51 h; Cmax was 239.54 ± 190.60 ng·mL-1; T1/2 was 5.16 ± 2.30 h; AUC0-t was 1439.85 ± 964.64 ng·mL-1·h. The AUC0-∞ was 1589.82 ± 1003.75 ng·mL-1·h. The purpose of this study was to develop a rapid and simple UPLC-MS/MS method to detect KPT-335 concentration in cat plasma and to conduct preliminary pharmacokinetic studies to support the future application of KPT-335 in felines.
摘要：
KPT-335（Verdinexor）是一种新型SINE，可有效抑制肿瘤细胞系的核蛋白Exportin1（XPO1/CRM1）并降低流感病毒的复制水平。KPT-335主要用于治疗犬肿瘤。目前，中国尚无有效治疗猫科动物肿瘤的药物。KPT-335可能具有治疗猫肿瘤的潜力。然而,KPT-335对猫的影响尚未报道，并且尚未建立用于药代动力学研究的相关方法。在这项研究中,开发了UPLC-MS/MS方法来测定猫血浆中KPT-335的浓度，其次是药代动力学研究。简而言之，血浆蛋白用乙腈沉淀，离心后收集上清液进行检测。猫血浆中KPT-335的线性范围为5-1,000ng/mL。获得了满意的准确度和精密度。日内准确率在-4.10%到10.48%之间,精度≤4.65%；日间精度在-0.11%和8.09%之间，精密度≤5.85%。日内和日间的准确性和精确度在监管范围内。初步药代动力学研究结果如下：Tmax为1.46±0.51h；Cmax为239.54±190.60ng·mL-1；T1/2为5.16±2.30h；AUC0-t为1439.85±964.64ng·mL-1·h。AUC0-∞为1589.82±1003.75ng·mL-1·h。本研究的目的是建立一种快速，简单的UPLC-MS/MS方法来检测猫血浆中KPT-335的浓度，并进行初步的药代动力学研究，以支持KPT-335在猫中的未来应用。
