Is aspirin a substrate of MDR1/P-glycoprotein?

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...

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Bibliographic Details
Published in:Xenobiotica 2020-10, Vol.50 (10), p.1258-1264
Main Authors: Singh, Renu, Naik, Tanvi, Nigam, Anuja, Chatterjee, Sagnik, Rajanna, Prabhakar, Shen, Hong, Iyer, Ramaswamy
Format: Article
Language:English
Subjects:
acetyl salicylic acid
Aspirin
DDI
MDR1
P-glycoprotein
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Summary: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.
ISSN:0049-8254
1366-5928
DOI:10.1080/00498254.2020.1757785