RT Journal Article SR Electronic T1 Esterase-like Activity of Human Serum Albumin Toward Prodrug Esters of Nicotinic Acid JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 395 OP 398 VO 25 IS 4 A1 Aline Salvi A1 Pierre-Alain Carrupt A1 Joachim M. Mayer A1 Bernard Testa YR 1997 UL http://dmd.aspetjournals.org/content/25/4/395.abstract AB The esterase-like activity of human serum albumin (HSA) toward esters of nicotinic acid was investigated under a variety of conditions such as protein concentration, temperature, pH, ionic strength, nature of buffers, and presence of organic solvents. Initial rate constants of hydrolysis of 18 nicotinates in the presence of 50 μM HSA were measured at pH 7.4 and 37°C. The substrates displayed half-lifes ranging from less than 15 min (2-butoxyethyl nicotinate) to more than 95 hr (methyl nicotinate). The hydrolysis of tert-butyl nicotinate was too slow to be measurable, whereas 1-carbamoylethyl nicotinate was stabilized against hydrolysis by the presence of HSA. The rate constants of HSA-catalyzed hydrolysis were well correlated (r2 = 0.85; N = 12) with previously published data obtained in human plasma, indicating similar substrate specificities in the two biological preparations. All evidence points to serum albumin as the possible major catalyst of hydrolysis of nicotinate esters in human plasma. The American Society for Pharmacology and Experimental Therapeutics