AI Article Synopsis
- This study investigates how aspirin (ASP) and indomethacin (IND) interact on a pharmacokinetic level using rat blood cells (RBCs) and liver cells (hepatocytes).
- In RBCs, aspirin and its breakdown product, salicylic acid (SA), increase indomethacin concentration while promoting its hydrolysis.
- In hepatocytes, low doses of IND are mainly glucuronidated (a type of metabolism), and the presence of ASP/SA inhibits this process, while higher doses lead to increased hydrolysis, suggesting that aspirin affects how indomethacin is processed and eliminated in the body.
Article Abstract
This study was conducted to explore the mechanism of the pharmacokinetic interaction between aspirin (ASP) and indomethacin (IND) using rat erythrocytes (RBCs) and hepatocytes. ASP was hydrolyzed to salicylic acid (SA) in both the RBCs and hepatocytes. Within RBCs, aspirin and/or salicylate (ASP/SA) increased the concentration of IND, accompanied by a constant hydrolysis of IND. In hepatocytes, a low dose of IND was subjected to glucuronidation rather than hydrolysis, and ASP/SA inhibited both the acylglucuronidation of IND and hydrolysis of IND glucuronide. A high dose of IND underwent hydrolysis with about double the glucuronidation, and ASP/SA decreased the ratio of hydrolysis to glucuronidation, accompanied by a loss of ASP, IND and their metabolites from the medium. Collectively, the results provide metabolic insight into the mechanism of drug-drug interaction between ASP/SA and IND in the hepatocytes and RBCs.
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| http://dx.doi.org/10.1248/bpb.26.675 | DOI Listing |
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