Vickers S, Duncan C A, White S D, Breault G O, Royds R B, de Schepper P J, Tempero K F
Drug Metab Dispos. 1978 Nov-Dec;6(6):640-6.
The succinimidoethyl (Sm) and pivaloyloxyethyl (P) esters of methyldopa were evaluated as progenitors of the latter. Experiments in spontaneously hypertensive (SH) rats and humans demonstrated that a radioactive dose of progenitor was well absorbed. The metabolism of these progenitors appeared to be comparable in the SH rat; the urinary excretion of [3H]methyldopa was similar after oral administration of [3H]Sm or [3H]P. In humans the levels of [3H]methyldopa were higher in the urine following administration of [3H]P. Apparently Sm was more resistant than P to extrahepatic esterase action in man (and dog). In man the catechol nucleus of Sm was apparently conjugated prior to hydrolytic cleavage to release conjugated [3H]methyidopa. The progenitors possessed similar antihypertensive properties in the SH rat but preliminary results in humans suggested that Sm possessed less antihypertensive potency than P.
甲基多巴的琥珀酰亚胺基乙酯（Sm）和特戊酰氧基乙酯（P）被评估为甲基多巴的前体药物。在自发性高血压（SH）大鼠和人体中进行的实验表明，放射性剂量的前体药物吸收良好。这些前体药物在SH大鼠中的代谢情况似乎相当；口服[3H]Sm或[3H]P后，[3H]甲基多巴的尿排泄量相似。在人体中，服用[3H]P后尿液中[3H]甲基多巴的水平更高。显然，在人体（和犬类）中，Sm比P对肝外酯酶作用更具抗性。在人体中，Sm的儿茶酚核显然在水解裂解之前就已结合，从而释放出结合型[3H]甲基多巴。这些前体药物在SH大鼠中具有相似的降压特性，但人体的初步结果表明，Sm的降压效力低于P。
