Empros Pharma AB, Solna, Sweden.
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Clin Pharmacol Drug Dev. 2021 Oct;10(10):1242-1247. doi: 10.1002/cpdd.920. Epub 2021 Feb 13.
The safety of a novel modified-release oral capsule with orlistat and acarbose (MR-OA) was investigated in 67 obese middle-aged White men with a body mass index of 32 to 40 kg/m or 30 to 32 kg/m plus waist circumference >102 cm. The purpose of this investigation was to compare MR-OA with the existing conventional orlistat regarding systemic safety defined as plasma orlistat concentration at the end of the treatment period of 14 days. Participants took the MR-OA fixed-dose combination formulation 3 times a day together with a major meal. Three different doses of MR-OA were evaluated-60/20, 90/30, and 120/40 (mg orlistat/mg acarbose)-as well as 1 reference group who received the conventional orlistat, Xenical, with 120 mg of orlistat. Blood plasma was sampled on days 1 and 14. The orlistat plasma concentrations of the MR-OA dose showed a delayed absorption and were lower compared with conventional orlistat at the end of the study. All doses were safe and well tolerated without any unexpected adverse events and no serious adverse events. The delay in the rise of orlistat plasma concentration indicates that the modified-release properties of the MR-OA formulation are effective. The systemic exposure of orlistat resulting from MR-OA was similar, albeit a bit lower than the conventional orlistat with 120 mg of orlistat. We can therefore assume that the safety profile regarding the orlistat moiety of MR-OA is comparable to the conventional orlistat and a promising approach for weight control in obese patients. Further clinical evaluation is underway.
一项针对一种新型奥利司他和阿卡波糖改良释放口服胶囊（MR-OA）的安全性研究，纳入了 67 名肥胖的中年白人男性，他们的体重指数（BMI）为 32 至 40kg/m2 或 30 至 32kg/m2 且腰围＞102cm。本研究旨在比较 MR-OA 与现有的常规奥利司他，评估其全身安全性，定义为治疗 14 天后的血浆奥利司他浓度。参与者每天服用 MR-OA 固定剂量组合制剂 3 次，与主餐一起服用。评估了三种不同剂量的 MR-OA，即 60/20、90/30 和 120/40（mg 奥利司他/mg 阿卡波糖），以及一个接受常规奥利司他（Xenical，120mg 奥利司他）的参考组。在第 1 天和第 14 天采集血样。MR-OA 剂量的奥利司他血浆浓度显示吸收延迟，且在研究结束时低于常规奥利司他。所有剂量均安全且耐受良好，无意外不良事件，也无严重不良事件。奥利司他血浆浓度升高延迟表明，MR-OA 制剂的改良释放特性是有效的。MR-OA 产生的奥利司他全身暴露与常规奥利司他（120mg）相似，尽管略低。因此，我们可以假设，MR-OA 中奥利司他部分的安全性与常规奥利司他相当，是肥胖患者体重控制的一种有前景的方法。进一步的临床评估正在进行中。
