Excipients, considered “inactive ingredients,” are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar to high-micromolar concentration. Another 109 activities were identified by testing against clinical safety targets. In cellular models, five excipients had fingerprints predictive of system-level toxicity. Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency, including brain and gut exposure of thimerosal and its major metabolite, which had dopamine D3 receptor dissociation constant K_d values of 320 and 210 nM, respectively. Although most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets.

赋形剂被认为是“非活性成分”，是配制药物的主要成分，并在其药代动力学中发挥关键作用。尽管它们无处不在，但尚未系统地研究它们是否在任何目标上都活跃。我们计算了批准的赋形剂与分子靶标结合的可能性。体外测试显示25种赋形剂活性，范围从低纳摩尔浓度到高微摩尔浓度。通过针对临床安全目标进行测试，确定了另外109个活动。在细胞模型中，五种赋形剂的指纹可预测系统水平的毒性。对7种赋形剂的暴露进行了调查，在某些人群中，其中2种可能达到体外靶标水平，包括硫柳汞及其主要代谢产物的脑和肠暴露，K _d值分别为320和210 nM。尽管大多数赋形剂应具有惰性，但许多批准的赋形剂可能直接调节生理相关靶标。