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During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on\u2010line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion\u2010based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter\u2010scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated \u03b3\u2010cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4\u2010mediated\n                    <jats:italic>N<\/jats:italic>\n                    \u2010demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost\u2010effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450\u2010mediated metabolic steps within early stages of the development of a new drug.\n                  <\/jats:p>","DOI":"10.1002\/elps.201400356","type":"journal-article","created":{"date-parts":[[2014,11,8]],"date-time":"2014-11-08T05:06:28Z","timestamp":1415423188000},"page":"1349-1357","source":"Crossref","is-referenced-by-count":29,"title":["Optimized on\u2010line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes"],"prefix":"10.1002","volume":"36","author":[{"given":"Roman","family":"\u0158em\u00ednek","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Science and CEITEC\u2014Central European Institute of Technology, Masaryk University  Brno Czech Republic"},{"name":"Clinical Pharmacology Laboratory Institute for Infectious Diseases, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zden\u011bk","family":"Glatz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Science and CEITEC\u2014Central European Institute of Technology, Masaryk University  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Thormann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Laboratory Institute for Infectious Diseases, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.v05n0202"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.59566\/IJBS.2006.2085"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-022X(02)00124-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(96)00244-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.02.051"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201200127"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200305636"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2003.12.025"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200500492"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200700475"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900373"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201100366"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201300294"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201300108"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201300124"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-27447-2_10"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-74806-9_15"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009337941"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.02.010"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2008.00972.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.70.6.777"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900221"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2010.06.028"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900703"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201100095"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2012.685777"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)90508-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2001.11927725"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470057780"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199212000-00022"},{"key":"e_1_2_8_32_1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0090-9556(24)15358-5","volume":"28","author":"Houston J. 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