Nigrovic V, Pandya J B, Auen M, Wajskol A
Anesth Analg. 1985 Nov;64(11):1047-52.
The contribution of enzyme-catalyzed hydrolysis to inactivation of atracurium in human and rat plasma was determined in vitro by inhibiting the enzyme carboxylesterase with triorthotolyl phosphate. The inhibitor was removed by centrifugation and aspiration. Atracurium was then added to both the control and the inhibited plasma samples, and all samples were incubated at 37 degrees C for 45 min. The amount of atracurium present in aliquots of plasma was determined using a bioassay technique in anesthetized rats. Inactivation of atracurium proceeded rapidly in control rat plasma but was markedly slowed in samples treated with the inhibitor of carboxylesterase. In contrast, the inactivation was slow in control human plasma, and inhibition of carboxylesterase produced only marginal, if any, effects. We conclude that the inactivation of atracurium proceeds, in part, by enzyme-catalyzed ester hydrolysis. In species with high enzyme activity in plasma, e.g., the rat, enzyme-catalyzed hydrolysis is clearly evident. In humans, the level of enzyme activity is low and the contribution of enzyme-catalyzed inactivation is less manifest. By exclusion, Hofmann elimination or other reactions probably represent the major inactivation pathway in humans.
通过用磷酸三邻甲苯酯抑制羧酸酯酶，在体外测定了酶催化水解对阿曲库铵在人和大鼠血浆中失活的作用。通过离心和抽吸去除抑制剂。然后将阿曲库铵添加到对照血浆样品和受抑制的血浆样品中，所有样品在37℃孵育45分钟。使用生物测定技术在麻醉大鼠中测定血浆等分试样中阿曲库铵的含量。阿曲库铵在对照大鼠血浆中迅速失活，但在用羧酸酯酶抑制剂处理的样品中明显减慢。相反，在对照人血浆中失活缓慢，羧酸酯酶的抑制仅产生微小的影响（如果有影响的话）。我们得出结论，阿曲库铵的失活部分是通过酶催化的酯水解进行的。在血浆中酶活性高的物种，如大鼠中，酶催化的水解明显可见。在人类中，酶活性水平低，酶催化失活的作用不太明显。通过排除法，霍夫曼消除或其他反应可能是人类主要的失活途径。
