Aspirin (acetyl salicylic acid) is widely used co-medication in patients with cardiovascular and cerebrovascular diseases. Given the prevalence of acetyl salicylic acid’s use as a co-medication and conflicting reports in the literature on it being a substrate of P-glycoprotein (P-gp). There is a potential risk for its interaction with compounds with P-gp liability, therefore, we have conducted a detailed investigation to determine substrate potential of acetyl salicylic acid towards P-gp.

We observed significantly lower cellular uptake of acetyl salicylic acid in MDR1 transfected LLC-PK1 cells compared to LLC-PK1 wild-type (WT) cells, however, the in vitro efflux of acetyl salicylic acid in MDR1 transfected LLC-PK1 cells was not inhibited by known inhibitors under various conditions. Acetyl salicylic acid did not show active asymmetrical transport across MDR1 transfected LLC-PK1 cells compared to LLC-PK1-WT cells in transwell assay. Moreover, no difference in plasma and brain exposure of acetyl salicylic acid and its metabolite salicylic acid was observed between FVB-WT and Mdr1a/b knockout (KO) mice.

Taken together, our findings indicate that acetyl salicylic acid is not a substrate of P-gp.

阿司匹林（乙酰水杨酸）被广泛用于心血管和脑血管疾病的患者。考虑到乙酰水杨酸作为一种共同用药的普遍现象，并且在文献中有报道称其为P-糖蛋白（P-gp）的底物。与具有P-gp责任的化合物发生相互作用存在潜在的风险，因此，我们进行了详细的研究，以确定乙酰水杨酸对P-gp的底物潜力。

我们观察到，与LLC-PK1野生型（WT）细胞相比，MDR1转染的LLC-PK1细胞中乙酰水杨酸的细胞摄取显着降低，但是，乙酰水杨酸在MDR1转染的LLC-PK1细胞中的体外流出未受到抑制在各种条件下被已知的抑制剂。与transwell分析中的LLC-PK1-WT细胞相比，乙酰水杨酸在MDR1转染的LLC-PK1细胞之间没有显示出主动的不对称转运。此外，在FVB-WT和Mdr1a / b基因敲除（KO）小鼠之间，未发现血浆和脑中乙酰水杨酸及其代谢产物水杨酸的暴露差异。

综上所述，我们的发现表明乙酰水杨酸不是P-gp的底物。