PT - JOURNAL ARTICLE AU - Fatma Goksin Bahar AU - Teruko Imai TI - Aspirin Hydrolysis in Human and Experimental Animal Plasma and the Effect of Metal Cations on Hydrolase Activities AID - 10.1124/dmd.113.051805 DP - 2013 Jul 01 TA - Drug Metabolism and Disposition PG - 1450--1456 VI - 41 IP - 7 4099 - http://dmd.aspetjournals.org/content/41/7/1450.short 4100 - http://dmd.aspetjournals.org/content/41/7/1450.full SO - Drug Metab Dispos2013 Jul 01; 41 AB - The hydrolyzing properties of plasma esterases for aspirin were investigated in human plasma and plasma from experimental animals. The observed rates of aspirin hydrolysis were in the following order: rabbit > human > monkey > rat > mouse > dog > minipig. In human, monkey, and dog plasma, aspirin was hydrolyzed by their major hydrolases, paraoxonase (PON), butyrylcholinesterase (BChE), and albumin. In rabbit, mouse, and rat plasma, carboxylesterase (CES) was determined to be the enzyme responsible for aspirin hydrolysis, and in mouse and rat plasma, especially the latter, hydrolase activity was increased by the addition of ethopropazine, a specific inhibitor of BChE. Interestingly, divalent cations affected the plasma activity by enhancing or inhibiting the hydrolase activity of plasma BChE. The addition of 2 mM calcium increased the hydrolysis of aspirin in human, monkey, and dog plasma by 2.7-, 1.9-, and 2.3-fold, respectively. Magnesium showed a similar but lesser effect. Increasing concentrations of calcium and magnesium resulted in a two-phase stimulatory effect on aspirin hydrolysis in human plasma. In contrast, the addition of zinc had an inhibitory effect on plasma BChE activity. It is postulated that calcium and magnesium bind to BChE and thereby change the conformation of the enzyme to a more appropriate position for aspirin hydrolysis.