Zeng Yuhong, Naik Subhashchandra, Tran Timothy, Wuthrich Philip, Muni Neal, Mahoney Robert P
Comera Life Sciences, Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, USA.
Comera Life Sciences, Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, USA.
J Pharm Sci. 2023 Nov;112(11):2933-2937. doi: 10.1016/j.xphs.2023.07.023. Epub 2023 Jul 28.
Caffeine is a novel excipient that effectively reduces viscosity of high concentration mAb formulations intended for subcutaneous (SQ) delivery. Two preclinical studies were conducted in rats to evaluate pharmacokinetic (PK) parameters of caffeine as well as its effects on the PK profile of a model mAb, namely ipilimumab. Results show that SQ absorption and elimination of caffeine was rapid, with the average T of 0.4 h and T of 1.6 h, administered with or without ipilimumab. Furthermore, caffeine did not affect ipilimumab SQ PK profiles. Independent of caffeine concentration, ipilimumab serum T was between 2 and 3 days, T was between 3 and 4 days and SQ bioavailability was about 64%. In addition, SQ injection of caffeine at different dose levels showed no irritation at the injection site or adverse effects. Results from the current PK studies warrant further development of caffeine as a viscosity reducing excipient for mAb SQ formulations.
咖啡因是一种新型辅料，可有效降低用于皮下注射的高浓度单克隆抗体制剂的粘度。在大鼠中进行了两项临床前研究，以评估咖啡因的药代动力学（PK）参数及其对模型单克隆抗体（即伊匹木单抗）PK曲线的影响。结果表明，无论是否与伊匹木单抗一起给药，皮下注射咖啡因的吸收和消除都很快，平均达峰时间（Tmax）为0.4小时，消除半衰期（T1/2）为1.6小时。此外，咖啡因不影响伊匹木单抗的皮下PK曲线。与咖啡因浓度无关，伊匹木单抗的血清达峰时间在2至3天之间，消除半衰期在3至4天之间，皮下生物利用度约为64%。此外，不同剂量水平的皮下注射咖啡因在注射部位未显示刺激或不良反应。当前PK研究的结果证明，咖啡因作为单克隆抗体皮下制剂的降粘辅料值得进一步开发。
