Is aspirin a substrate of MDR1/P-glycoprotein?. (2nd October 2020)

• Record Type: Journal Article
• Authors: Singh, Renu; Naik, Tanvi; Nigam, Anuja; Chatterjee, Sagnik; Rajanna, Prabhakar; Shen, Hong; Iyer, Ramaswamy
• Is Part Of: Xenobiotica. Volume 50:Number 10(2020:Oct.)
• Page Start: 1258
• Page End: 1264
• Publication Date: 2020-10-02
• Subjects: Aspirin -- acetyl salicylic acid -- P-glycoprotein -- MDR1 -- DDI; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2020.1757785
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 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.