Quon C Y, Stampfli H F
Drug Metab Dispos. 1985 Jul-Aug;13(4):420-4.
The blood esterase mediating the hydrolysis of esmolol was characterized in several different species including man. In contrast to most ester-containing drugs, hydrolysis of esmolol was mediated by an esterase in the cytosol of red blood cells (RBC) in man and dogs and not in plasma or RBC membrane. Species differences in the esterase activity existed. Guinea pig and rat blood esterase activities were much greater than those in the dog followed by those in man. In addition, the esterase activity in rat and guinea pig blood was localized in plasma and not in RBC. Purified human serum cholinesterase, human RBC membrane acetylcholinesterase, human hemoglobin, human carbonic anhydrases A and B, and human and dog serum albumin were all inactive against esmolol. Esmolol esterase activity in human and dog blood was inhibited by sodium fluoride, EDTA, and p-hydroxymercuribenzoate, but not by echothiophate, eserine, and acetazolamide. In contrast, echothiophate and sodium fluoride, but not eserine, inhibited the esterase activity in rat and guinea pig plasma. Metabolic interaction studies indicated that acetylcholine, succinylcholine, procaine, and chloroprocaine did not interfere with the metabolism of esmolol by human and dog blood. Based on the results, it appeared that an arylesterase in human and dog RBC cytosol mediated the hydrolysis of esmolol while an aliphatic esterase mediated the hydrolysis of esmolol in guinea pig and rat plasma.
在包括人类在内的几种不同物种中对介导艾司洛尔水解的血液酯酶进行了特性研究。与大多数含酯类药物不同，在人和狗中，艾司洛尔的水解是由红细胞（RBC）胞质溶胶中的一种酯酶介导的，而非血浆或红细胞膜中的酯酶。酯酶活性存在物种差异。豚鼠和大鼠的血液酯酶活性远高于狗，其次是人类。此外，大鼠和豚鼠血液中的酯酶活性定位于血浆而非红细胞中。纯化的人血清胆碱酯酶、人红细胞膜乙酰胆碱酯酶、人血红蛋白、人碳酸酐酶A和B以及人和狗的血清白蛋白对艾司洛尔均无活性。人和狗血液中的艾司洛尔酯酶活性受到氟化钠、乙二胺四乙酸（EDTA）和对羟基汞苯甲酸的抑制，但不受依可碘酯、毒扁豆碱和乙酰唑胺的抑制。相比之下，依可碘酯和氟化钠可抑制大鼠和豚鼠血浆中的酯酶活性，但毒扁豆碱则无此作用。代谢相互作用研究表明，乙酰胆碱、琥珀酰胆碱、普鲁卡因和氯普鲁卡因不会干扰人和狗血液对艾司洛尔的代谢。根据这些结果，似乎人和狗红细胞胞质溶胶中的一种芳基酯酶介导了艾司洛尔的水解，而豚鼠和大鼠血浆中的一种脂肪族酯酶介导了艾司洛尔的水解。
