In vitro evaluation of the inhibitory potential of pharmaceutical excipients on human carboxylesterase 1A and 2.
In vitro evaluation of the inhibitory potential of pharmaceutical excipients on human carboxylesterase 1A and 2.
复制标题
药用辅料对人羧酸酯酶1A和2抑制潜力的体外评价。
DOI：
10.1371/journal.pone.0093819
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Zhang C;Xu Y;Zhong Q;Li X;Gao P;Feng C;Chu Q;Chen Y;Liu D
Two major forms of human carboxylesterase (CES), CES1A and CES2, dominate the pharmacokinetics of most prodrugs such as imidapril and irinotecan (CPT-11). Excipients, largely used as insert vehicles in formulation, have been recently reported to affect drug enzyme activity. The influence of excipients on the activity of CES remains undefined. In this study, the inhibitory effects of 25 excipients on the activities of CES1A1 and CES2 were evaluated. Imidapril and CPT-11 were used as substrates and cultured with liver microsomes in vitro. Imidapril hydrolase activities of recombinant CES1A1 and human liver microsomes (HLM) were strongly inhibited by sodium lauryl sulphate (SLS) and polyoxyl 40 hydrogenated castor oil (RH40) [Inhibition constant (Ki) = 0.04±0.01 μg/ml and 0.20±0.09 μg/ml for CES1A1, and 0.12±0.03 μg/ml and 0.76±0.33 μg/ml, respectively, for HLM]. The enzyme hydrolase activity of recombinant CES2 was substantially inhibited by Tween 20 and polyoxyl 35 castor oil (EL35) (Ki = 0.93±0.36 μg/ml and 4.4±1.24 μg/ml, respectively). Thus, these results demonstrate that surfactants such as SLS, RH40, Tween 20 and EL35 may attenuate the CES activity; such inhibition should be taken into consideration during drug administration.
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影响因子：
6.1
作者：
Blonder, JM;Baird, L;Rosenthal, GJ
通讯作者：
Rosenthal, GJ
DOI：
10.1016/j.ejpb.2006.07.007
发表时间：
2007-01-01
影响因子：
4.9
作者：
Ahuja, Naveen;Katare, Om Prakash;Singh, Bhupinder
通讯作者：
Singh, Bhupinder
DOI：
10.1007/bf03259937
发表时间：
1988-03-01
期刊：
MEDICAL TOXICOLOGY AND ADVERSE DRUG EXPERIENCE
影响因子：
--
作者：
GOLIGHTLY, LK;SMOLINSKE, SS;RUMACK, BH
通讯作者：
RUMACK, BH
影响因子：
5.8
作者：
JOHNSTON, TP;PALMER, WK
通讯作者：
PALMER, WK
影响因子：
3
作者：
Johnston, TP;Baker, JC;Palmer, WK
通讯作者：
Palmer, WK