Winkle R A, Meffin P J, Ricks W B, Harrison D C
Br J Clin Pharmacol. 1977 Oct;4(5):519-22. doi: 10.1111/j.1365-2125.1977.tb00779.x.
1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady-state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/- 1.0. 4 Previous studies using non-specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.
我们使用一种针对每种物质的新检测方法,测量了接受该药物长期口服治疗的患者体内醋丁洛尔及其主要代谢物的血浆浓度。我们的研究表明:
在所有七名受试者的给药间隔期间,乙酰代谢物的浓度在任何时候都高于醋丁洛尔的浓度。
乙酰代谢物与未变化的醋丁洛尔的平均稳态血浆浓度之比为2.7±1.0。
先前使用非特异性方法将乙酰代谢物和醋丁洛尔的血浆浓度作为单一物质进行测量的研究,不能用于确定药代动力学参数,也不能提供血浆药物浓度与效应之间的可靠相关性。
未来测定醋丁洛尔血浆浓度的研究应考虑到这种代谢物。
有必要进一步开展工作,以确定该代谢物对醋丁洛尔在人体内作用的贡献。