{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T07:56:01Z","timestamp":1765526161407,"version":"3.48.0"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dmpt-2017-0036_s_999_w2aab2b8b7b1b7b1aab1c16b1Aa\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam\u2019s metabolic liver pathways and other pharmacokinetic features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2017-0036_s_998_w2aab2b8b7b1b7b1aab1c16b2Aa\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      To determine phenazepam\u2019s metabolic pathways, the study was divided into three stages:\n                      <jats:italic>in silico<\/jats:italic>\n                      modeling,\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiment (cell culture study), and\n                      <jats:italic>in vivo<\/jats:italic>\n                      confirmation.\n                      <jats:italic>In silico<\/jats:italic>\n                      modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      study was performed using a hepatocytes\u2019 cell culture, cultivated in a microbioreactor to produce cytochrome P450 isoenzymes. The culture medium contained specific cytochrome P450 isoforms inhibitors and substrates (for CYP2C9, CYP3A4, CYP2C19, and CYP2B6) to determine the cytochrome that was responsible for phenazepam\u2019s metabolism. We also measured CYP3A activity using the 6-betahydroxycortisol\/cortisol ratio in patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2017-0036_s_997_w2aab2b8b7b1b7b1aab1c16b3Aa\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      According to\n                      <jats:italic>in silico<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      analysis results, the most probable metabolizer of phenazepam is CYP3A4. By the\n                      <jats:italic>in vivo<\/jats:italic>\n                      study results, CYP3A activity decreased sufficiently (from 3.8 [95% CI: 2.94\u20134.65] to 2.79 [95% CI: 2.02\u20133.55], p=0.017) between the start and finish of treatment in patients who were prescribed just phenazepam.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2017-0036_s_996_w2aab2b8b7b1b7b1aab1c16b4Aa\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Experimental\n                      <jats:italic>in silico<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies confirmed that the original Russian benzodiazepine phenazepam was the substrate of CYP3A4 isoenzyme.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dmpt-2017-0036","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T18:16:04Z","timestamp":1525457764000},"page":"65-73","source":"Crossref","is-referenced-by-count":12,"title":["Which cytochrome P450 metabolizes phenazepam? Step by step\n                    <i>in silico<\/i>\n                    ,\n                    <i>in vitro<\/i>\n                    , and\n                    <i>in vivo<\/i>\n                    studies"],"prefix":"10.1515","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-7167","authenticated-orcid":false,"given":"Dmitriy V.","family":"Ivashchenko","sequence":"first","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia V.","family":"Rudik","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, 10 bldg. , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey A.","family":"Poloznikov","sequence":"additional","affiliation":[{"name":"Moscow Institute of Physics and Technology , 9 Institutsky lane, 141700 , Dolgoprudny , Russian Federation ; National Medical Research Radiological Center, Ministry of Health of the Russian Federation , Koroleva, 4 , 249036 Obninsk , Russian Federation ; SRC \u201cBioclinicum\u201d , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey V.","family":"Nikulin","sequence":"additional","affiliation":[{"name":"Moscow Institute of Physics and Technology , 9 Institutsky lane, 141700 , Dolgoprudny , Russian Federation ; National Medical Research Radiological Center, Ministry of Health of the Russian Federation , Koroleva, 4 , 249036 Obninsk , Russian Federation ; SRC \u201cBioclinicum\u201d , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy V.","family":"Smirnov","sequence":"additional","affiliation":[{"name":"National Research Center \u2013 Institute of Immunology Federal Medical-Biological Agency of Russia , Moscow , Russian Federation"},{"name":"I.M. Sechenov First Moscow State Medical University , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Tonevitsky","sequence":"additional","affiliation":[{"name":"Moscow Institute of Physics and Technology , 9 Institutsky lane, 141700 , Dolgoprudny , Russian Federation ; National Medical Research Radiological Center, Ministry of Health of the Russian Federation , Koroleva, 4 , 249036 Obninsk , Russian Federation ; SRC \u201cBioclinicum\u201d , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugeniy A.","family":"Bryun","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"},{"name":"Moscow Research Practical Center of Narcology , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitriy A.","family":"Sychev","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2018,5,4]]},"reference":[{"key":"2025121207100439963_j_dmpt-2017-0036_ref_001_w2aab2b8b7b1b7b1ab2b1b1Aa","unstructured":"Seredenin SB, Voronina TA, Neznamov GG, Zherdev VP. Phenazepam. 25 years in medical practice. Moscow: Nauka, 2007 [in Russian]."},{"key":"2025121207100439963_j_dmpt-2017-0036_ref_002_w2aab2b8b7b1b7b1ab2b1b2Aa","unstructured":"Phenazepam. Pre-review report. Expert committee on drug dependence, thirty-seventh meeting, Geneva. 2015. http:\/\/www.who.int\/medicines\/access\/controlled-substances\/5.8_Phenazepam_PR1.pdf?ua=1. Accessed 20 Jul 2017."},{"key":"2025121207100439963_j_dmpt-2017-0036_ref_003_w2aab2b8b7b1b7b1ab2b1b3Aa","doi-asserted-by":"crossref","unstructured":"Maskell PD, De Paoli G, Seetohul LN, Pounder DJ. Phenazepam: the drug that came in from the cold. J Forensic Legal Med 2012;19:122\u20135.","DOI":"10.1016\/j.jflm.2011.12.014"},{"key":"2025121207100439963_j_dmpt-2017-0036_ref_004_w2aab2b8b7b1b7b1ab2b1b4Aa","doi-asserted-by":"crossref","unstructured":"Lomas EC, Maskell PD. Phenazepam: more information coming in from the cold. 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