Dobrinska M R, Welling P G
J Pharm Sci. 1977 May;66(5):688-92. doi: 10.1002/jps.2600660520.
The pharmacokinetics of methsuximide and its major metabolite 2-methyl-2-phenylsuccinimide were studied in dogs after single intravenous doses. Plasma methsuximide levels were described by a two-compartment open model, and those of the metabolite were described by a one-compartment open model. An expression was derived that describes both methsuximide and metabolite plasma levels after methsuximide administration. Excellent fits were obtained between observed data and those predicted from the model. The metabolite accounted for 40% of the overall elimination of methsuximide, and the half-life of the metabolite (15 hr) was much greater than that of the parent drug (1--3.5 hr). The results suggest that pharmacological effects after methsuximide administration may be due primarily to the metabolite, which may accumulate in the body during repeated doses.
单次静脉注射给药后，在犬体内研究了甲琥胺及其主要代谢产物2-甲基-2-苯基琥珀酰亚胺的药代动力学。甲琥胺血浆水平用二室开放模型描述，代谢产物血浆水平用一室开放模型描述。推导得到一个表达式，用于描述甲琥胺给药后甲琥胺和代谢产物的血浆水平。观察数据与模型预测值之间拟合良好。代谢产物占甲琥胺总消除量的40%，代谢产物的半衰期（15小时）远长于母体药物的半衰期（1-3.5小时）。结果表明，甲琥胺给药后的药理作用可能主要归因于代谢产物，在重复给药期间该代谢产物可能在体内蓄积。
