{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T22:05:51Z","timestamp":1768255551673,"version":"3.49.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T00:00:00Z","timestamp":1396483200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0093819","type":"journal-article","created":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T16:51:22Z","timestamp":1396543882000},"page":"e93819","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["In Vitro Evaluation of the Inhibitory Potential of Pharmaceutical Excipients on Human Carboxylesterase 1A and 2"],"prefix":"10.1371","volume":"9","author":[{"given":"Chengliang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjiao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoni","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengyang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,4,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.addr.2007.08.017","article-title":"The effects of pharmaceutical excipients on drug disposition","volume":"59","author":"TR Buggins","year":"2007","journal-title":"Adv Drug Deliv Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tox.2004.02.017","article-title":"Flow-cytometric analysis on adverse effects of polysorbate 80 in rat thymocytes","volume":"199","author":"S Hirama","year":"2004","journal-title":"Toxicology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"F392","DOI":"10.1136\/adc.2009.160192","article-title":"Safety of \u201cinert\u201d additives or excipients in paediatric medicines","volume":"94","author":"MC Nahata","year":"2009","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/toxsci\/kfq207","article-title":"Comprehensive investigation of hydroxypropyl methylcellulose, propylene glycol, polysorbate 80, and hydroxypropyl-beta-cyclodextrin for use in general toxicology studies","volume":"117","author":"EA Thackaberry","year":"2010","journal-title":"Toxicol Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ijpharm.2009.06.018","article-title":"The effects of common solubilizing agents on the intestinal membrane barrier functions and membrane toxicity in rats","volume":"379","author":"KA Hamid","year":"2009","journal-title":"Int J Pharm"},{"key":"ref6","unstructured":"EMA (2005) Reflection paper: formulations of choice for the paediatric population. EMA\/CHMP\/PEG\/194810\/2005."},{"key":"ref7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.yrtph.2011.02.010","article-title":"Excipients in medicinal products used in gastroenterology as a possible cause of side effects","volume":"60","author":"MG Ursino","year":"2011","journal-title":"Regul Toxicol Pharmacol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijpharm.2004.03.001","article-title":"Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo","volume":"278","author":"G Cornaire","year":"2004","journal-title":"Int J Pharm"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1248\/bpb.30.1301","article-title":"Effects of Labrasol and other pharmaceutical excipients on the intestinal transport and absorption of rhodamine123, a P-glycoprotein substrate, in rats","volume":"30","author":"Y Lin","year":"2007","journal-title":"Biol Pharm Bull"},{"key":"ref10","first-page":"319","article-title":"Lipid excipients Peceol and Gelucire 44\/14 decrease P-glycoprotein mediated efflux of rhodamine 123 partially due to modifying P-glycoprotein protein expression within Caco-2 cells","volume":"10","author":"K Sachs-Barrable","year":"2007","journal-title":"J Pharm Pharm Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1211\/jpp.60.12.0009","article-title":"Modulating effect of polyethylene glycol on the intestinal transport and absorption of prednisolone, methylprednisolone and quinidine in rats by in-vitro and in-situ absorption studies","volume":"60","author":"Q Shen","year":"2008","journal-title":"J Pharm Pharmacol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijpharm.2006.01.020","article-title":"Modulation of intestinal P-glycoprotein function by polyethylene glycols and their derivatives by in vitro transport and in situ absorption studies","volume":"313","author":"Q Shen","year":"2006","journal-title":"Int J Pharm"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/jps.20017","article-title":"Modulation of intestinal P-glycoprotein function by cremophor EL and other surfactants by an in vitro diffusion chamber method using the isolated rat intestinal membranes","volume":"93","author":"Y Shono","year":"2004","journal-title":"J Pharm Sci"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.ejps.2009.05.001","article-title":"Effects of polyoxyethylene (40) stearate on the activity of P-glycoprotein and cytochrome P450","volume":"37","author":"S Zhu","year":"2009","journal-title":"Eur J Pharm Sci"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1021\/mp3001815","article-title":"Pharmaceutical excipients influence the function of human uptake transporting proteins","volume":"9","author":"A Engel","year":"2012","journal-title":"Mol Pharm"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/bdd.383","article-title":"In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam","volume":"25","author":"RC Bravo Gonzalez","year":"2004","journal-title":"Biopharm Drug Dispos"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ejps.2008.11.002","article-title":"Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo","volume":"36","author":"X Ren","year":"2009","journal-title":"Eur J Pharm Sci"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2133\/dmpk.21.173","article-title":"Human carboxylesterase isozymes: catalytic properties and rational drug design","volume":"21","author":"T Imai","year":"2006","journal-title":"Drug Metab Pharmacokinet"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1517\/13543776.2011.586339","article-title":"Carboxylesterase inhibitors","volume":"21","author":"MJ Hatfield","year":"2011","journal-title":"Expert Opin Ther Pat"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/dmd.30.5.488","article-title":"Current progress on esterases: from molecular structure to function","volume":"30","author":"T Satoh","year":"2002","journal-title":"Drug Metab Dispos"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1124\/dmd.110.034454","article-title":"In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic drugs on human carboxylesterase activities","volume":"38","author":"T Fukami","year":"2010","journal-title":"Drug Metab Dispos"},{"key":"ref22","unstructured":"Xu YJ, Zhang CL, Li Xiping, Wu Tao, Ren XH, <etal>et al<\/etal>.. (2013) Evaluation of the inhibitory effects of antihypertensive drugs on human carboxylesterase in vitro. Drug Metab Pharmacokinet."},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1002\/jps.21376","article-title":"Allosteric kinetics of human carboxylesterase 1: species differences and interindividual variability","volume":"97","author":"S Takahashi","year":"2008","journal-title":"J Pharm Sci"},{"key":"ref24","first-page":"1189","article-title":"Characterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2","volume":"60","author":"R Humerickhouse","year":"2000","journal-title":"Cancer Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1007\/s11596-012-1037-z","article-title":"Dexamethasone regulates differential expression of carboxylesterase 1 and carboxylesterase 2 through activation of nuclear receptors","volume":"32","author":"CL Zhang","year":"2012","journal-title":"J Huazhong Univ Sci Technolog Med Sci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1124\/dmd.109.026567","article-title":"Human arylacetamide deacetylase is a principal enzyme in flutamide hydrolysis","volume":"37","author":"A Watanabe","year":"2009","journal-title":"Drug Metab Dispos"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1124\/dmd.108.024331","article-title":"Different inhibitory effects in rat and human carboxylesterases","volume":"37","author":"S Takahashi","year":"2009","journal-title":"Drug Metab Dispos"},{"key":"ref28","first-page":"128","article-title":"Pharmaceutical excipients. Adverse effects associated with inactive ingredients in drug products (Part I)","volume":"3","author":"LK Golightly","year":"1988","journal-title":"Med Toxicol Adverse Drug Exp"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s11095-010-0170-2","article-title":"Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells","volume":"27","author":"L Tompkins","year":"2010","journal-title":"Pharm Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/0006-2952(93)90668-M","article-title":"Mechanism of poloxamer 407-induced hypertriglyceridemia in the rat","volume":"46","author":"TP Johnston","year":"1993","journal-title":"Biochem Pharmacol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1097\/00005344-199705000-00003","article-title":"Effect of poloxamer 407 on the activity of microsomal 3-hydroxy-3-methylglutaryl CoA reductase in rats","volume":"29","author":"TP Johnston","year":"1997","journal-title":"J Cardiovasc Pharmacol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0021-9150(99)00339-1","article-title":"Regression of poloxamer 407-induced atherosclerotic lesions in C57BL\/6 mice using atorvastatin","volume":"149","author":"TP Johnston","year":"2000","journal-title":"Atherosclerosis"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1097\/00005344-199912000-00010","article-title":"Potential downregulation of HMG-CoA reductase after prolonged administration of P-407 in C57BL\/6 mice","volume":"34","author":"TP Johnston","year":"1999","journal-title":"J Cardiovasc Pharmacol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"PL261","DOI":"10.1016\/S0024-3205(99)00495-6","article-title":"Dose-dependent hyperlipidemia in rabbits following administration of poloxamer 407 gel","volume":"65","author":"JM Blonder","year":"1999","journal-title":"Life Sci"},{"key":"ref35","first-page":"189","article-title":"Poloxamer 407-mediated alterations in the activities of enzymes regulating lipid metabolism in rats","volume":"6","author":"KM Wasan","year":"2003","journal-title":"J Pharm Pharm Sci"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jbt.20178","article-title":"Human carboxylesterases and their role in xenobiotic and endobiotic metabolism","volume":"21","author":"MK Ross","year":"2007","journal-title":"J Biochem Mol Toxicol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/03602530600952164","article-title":"Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes","volume":"39","author":"M Hosokawa","year":"2007","journal-title":"Drug Metab Rev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bcp.2009.08.019","article-title":"Transcriptional regulation of human carboxylesterase 1A1 by nuclear factor-erythroid 2 related factor 2 (Nrf2)","volume":"79","author":"T Maruichi","year":"2010","journal-title":"Biochem Pharmacol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1124\/dmd.107.015388","article-title":"Identification of rat and human cytochrome p450 isoforms and a rat serum esterase that metabolize the pyrethroid insecticides deltamethrin and esfenvalerate","volume":"35","author":"SJ Godin","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/bbrc.1997.6413","article-title":"Molecular cloning and characterization of a novel putative carboxylesterase, present in human intestine and liver","volume":"233","author":"H Schwer","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejpb.2006.07.007","article-title":"Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers","volume":"65","author":"N Ahuja","year":"2007","journal-title":"Eur J Pharm Biopharm"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jconrel.2003.11.004","article-title":"New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo","volume":"95","author":"AC Sintov","year":"2004","journal-title":"J Control Release"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ijpharm.2007.05.006","article-title":"Use of a screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design","volume":"342","author":"R Vandecruys","year":"2007","journal-title":"Int J Pharm"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.toxlet.2004.08.003","article-title":"Cremophor EL augments the cytotoxicity of hydrogen peroxide in lymphocytes dissociated from rat thymus glands","volume":"154","author":"K Iwase","year":"2004","journal-title":"Toxicol Lett"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0928-0987(02)00055-6","article-title":"Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers","volume":"16","author":"BD Rege","year":"2002","journal-title":"Eur J Pharm Sci"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.1002\/jat.833","article-title":"Carboxylesterase: specificity and spontaneous reactivation of an endogenous scavenger for organophosphorus compounds","volume":"21","author":"DM Maxwell","year":"2001","journal-title":"J Appl Toxicol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0093819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T09:29:50Z","timestamp":1540200590000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0093819"}},"subtitle":[],"editor":[{"given":"Alessio","family":"Lodola","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,4,3]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,4,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0093819","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,3]]}}}