{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:42:24Z","timestamp":1765546944507,"version":"3.48.0"},"reference-count":24,"publisher":"Walter de Gruyter GmbH","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dmpt-2022-0117_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Timolol maleate is used for the treatment of glaucoma and metabolized by cytochrome CYP2D6 in the liver. The aim of this study was the evaluation of the influence of\n                      <jats:italic>CYP2D6*4<\/jats:italic>\n                      and\n                      <jats:italic>CYP2D6*10<\/jats:italic>\n                      gene polymorphisms on the safety of medications containing 0.5% of timolol maleate as glaucoma treatment in patients with primary open-angle glaucoma (POAG).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2022-0117_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>105 patients with POAG were prescribed glaucoma medications, containing 0.5% timolol maleate. The safety of glaucoma treatment was determined by electrocardiography (ECG) (to assess heart rate (HR) and PQ interval) and blood pressure (BP) measurements. The real-time polymerase chain reaction method was used for the detection of single nucleotide polymorphisms (SNP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2022-0117_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The risk of adverse drug reactions was higher in patients with the\n                      <jats:italic>CYP2D6*4<\/jats:italic>\n                      \u00a0GA genotype compared with GG: mean HR change at 1\u00a0month (2.88\u00a0\u00b1\u00a04.68 and 6.44\u00a0\u00b1\u00a05.57, p&lt;0.001) and 6\u00a0months (5.14\u00a0\u00b1\u00a08.93 and 7.88\u00a0\u00b1\u00a05.65, p&lt;0.001), mean PQ interval change at 1 (0.01\u00a0\u00b1\u00a00.031 and 0.02\u00a0\u00b1\u00a00.022, p=0.003) and 6\u00a0months (0.01\u00a0\u00b1\u00a00.032 and 0.02\u00a0\u00b1\u00a00.024, p=0.003). The risk of adverse drug reactions was higher in patients with the\n                      <jats:italic>CYP2D6*10<\/jats:italic>\n                      CT genotype compared with CC: mean HR change at 1\u00a0month (2.94\u00a0\u00b1\u00a04.65 and 6.34\u00a0\u00b1\u00a05.66, p&lt;0.001) and 6\u00a0months (5.20\u00a0\u00b1\u00a08.90 and 7.78\u00a0\u00b1\u00a05.75, p&lt;0.001), mean PQ interval change at 1 (0.01\u00a0\u00b1\u00a00.032 and 0.02\u00a0\u00b1\u00a00.021, p=0.014) and 6\u00a0months (0.01\u00a0\u00b1\u00a00.033 and 0.02\u00a0\u00b1\u00a00.022, p=0.014).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2022-0117_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CYP2D6*4<\/jats:italic>\n                      and\n                      <jats:italic>CYP2D6*10<\/jats:italic>\n                      gene polymorphisms may affect a higher risk of timolol-induced bradycardia and increased PQ interval of treatment medications containing 0.5% of timolol maleate in patients with POAG.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dmpt-2022-0117","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T11:32:25Z","timestamp":1661340745000},"page":"143-148","source":"Crossref","is-referenced-by-count":6,"title":["Effect of\n                    <i>CYP2D6*4<\/i>\n                    ,\n                    <i>CYP2D6*10<\/i>\n                    polymorphisms on the safety of treatment with timolol maleate in patients with glaucoma"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5899-2714","authenticated-orcid":false,"given":"Larisa K.","family":"Moshetova","sequence":"first","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-7702","authenticated-orcid":false,"given":"Maria M.","family":"Soshina","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-7467","authenticated-orcid":false,"given":"Ksenia I.","family":"Turkina","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5621-8266","authenticated-orcid":false,"given":"Elena A.","family":"Grishina","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5166-7903","authenticated-orcid":false,"given":"Zhannet A.","family":"Sozaeva","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-4410","authenticated-orcid":false,"given":"Anastasia A.","family":"Kachanova","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-8520","authenticated-orcid":false,"given":"Kristina A.","family":"Akmalova","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-7167","authenticated-orcid":false,"given":"Dmitriy V.","family":"Ivashchenko","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"},{"name":"Penza Branch of Russian Medical Academy of Continuous Professional Education , Penza , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-9726","authenticated-orcid":false,"given":"Mikhail S.","family":"Zastrozhin","sequence":"additional","affiliation":[{"name":"Russian Medical Academy of Continuous Professional Education , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-5763","authenticated-orcid":false,"given":"Vladimir P.","family":"Fisenko","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University (Sechenov University) , Moscow , Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-3680","authenticated-orcid":false,"given":"Dmitry 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":[[2022,8,24]]},"reference":[{"key":"2025121207125697970_j_dmpt-2022-0117_ref_001","doi-asserted-by":"crossref","unstructured":"Udovichenko, EV, Zhirov, AL, Sorokin, EL. Unreasonable diagnosis of glaucoma and one-stage prescription of hypotensive therapy. Reflection 2019;9:40\u20133. https:\/\/doi.org\/10.25276\/2686-6986-2019-2-40-43.","DOI":"10.25276\/2686-6986-2019-2-40-43"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_002","doi-asserted-by":"crossref","unstructured":"Moshetova, LK, Soshina, MM, Sychev, DA, Turkina, KI. Pharmacogenetics of timolol. Vestn Oftalmol 2019;3:137\u201343. https:\/\/doi.org\/10.17116\/oftalma2019135031137.","DOI":"10.17116\/oftalma2019135031137"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_003","unstructured":"Avetisov, SE, Egorov, EA, Moshetova, LK, Neoroev, VV, Takhchidi, KP, editors. Ophthalmology: a national guide. Moscow: GEOTAR Media; 2013:716 p."},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_004","doi-asserted-by":"crossref","unstructured":"Moroi, SE, Raoof, DA, Reed, DM, Zollner, S, Qin, Z, Richards, JE. Progress toward personalized medicine for glaucoma. Expet Rev Ophthalmol 2009;4:145\u201361. https:\/\/doi.org\/10.1586\/eop.09.6.","DOI":"10.1586\/eop.09.6"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_005","doi-asserted-by":"crossref","unstructured":"Moshetova, LK, Soshina, MM, Sychev, DA, Turkina, KI. Practical pharmacogenetics for personalized management of glaucoma patients. Farmakogenetika i farmakogenomika. Pharmacogenet Genomics 2020:26\u201334. (In Russ). https:\/\/doi.org\/10.37489\/2588-0527-2020-1-26-34.","DOI":"10.37489\/2588-0527-2020-1-26-34"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_006","unstructured":"Egorov, EA, Egorov, AE. Beta-blockers in treatment of glaucoma. Back to the future. Literature review. RMJ Clinical Ophthalmology 2013;3:92."},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_007","unstructured":"Order of the ministry of health of the Russian federation of December 29, 2012 \u2116 1700n \u201cOn approval of the standard of primary health care for glaucoma\u201d [Online]. Available from: https:\/\/minzdrav.gov.ru\/documents\/8388-prikaz-ministerstva-zdravoohraneniya-rossiyskoy-federatsii-ot-29-dekabrya-2012-g-1700n-ob-utverzhdenii-standarta-pervichnoy-mediko-sanitarnoy-pomoschi-pri-glaukome."},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_008","unstructured":"Medical Expenditure Panel Survey (MEPS) 2013-2019. Agency for Healthcare Research and Quality (AHRQ) ClinCalc DrugStats Database version 2021.10 [Online]. Available from: https:\/\/clincalc.com\/DrugStats\/Drugs\/Timolol [Accessed 2022]."},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_009","unstructured":"Egorov, EA, Astakhov, YS, Yerichev, VP, editors. National guideline on glaucoma for practicing physicians, 3rd ed. Moscow: GEOTAR-Media; 2015:12 p."},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_010","doi-asserted-by":"crossref","unstructured":"Grieshaber, MC. Is the medication used to achieve the target intraocular pressure in glaucoma therapy of relevance? An exemplary analysis on the basis of two beta-blockers. Prog Retin Eye Res 2010;29:79\u201393. https:\/\/doi.org\/10.1016\/j.preteyeres.2009.08.002.","DOI":"10.1016\/j.preteyeres.2009.08.002"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_011","doi-asserted-by":"crossref","unstructured":"Laverty, R. Catecholamines: role in health and disease. Drugs 1978;16:418\u201340. https:\/\/doi.org\/10.2165\/00003495-197816050-00003.","DOI":"10.2165\/00003495-197816050-00003"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_012","doi-asserted-by":"crossref","unstructured":"Leier, CV, Baker, ND, Weber, PA. Cardiovascular effects of ophthalmic timolol. Ann Intern Med 1986;104:197\u20139. https:\/\/doi.org\/10.7326\/0003-4819-104-2-197.","DOI":"10.7326\/0003-4819-104-2-197"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_013","unstructured":"Valvo, E, Gammaro, L, Tessitore, N, Fabris, A, Ortalda, V, Bedogna, V, et al.. Effects of timolol on blood pressure, systemic hemodynamics, plasma renin activity, and glomerular filtration rate in patients with essential hypertension. J Clin Pharmacol Ther Toxicol 1984;22:156\u201361."},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_014","doi-asserted-by":"crossref","unstructured":"Alvan, G, Calissendorf, B, Seideman, P, Wildmark, K, Wildmark, G. Absorbtion of ocular timolol. Clin Pharmocokinet 1980;5:95\u2013100. https:\/\/doi.org\/10.2165\/00003088-198005010-00004.","DOI":"10.2165\/00003088-198005010-00004"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_015","doi-asserted-by":"crossref","unstructured":"Korte, JM, Kaila, T, Saari, KM. Systemic bioavailability and cardiopulmonary effects of 0.5% timolol eyedrops. Graefes Arch Clin Exp Ophthalmol 2002;240:430\u20135. https:\/\/doi.org\/10.1007\/s00417-002-0462-2.","DOI":"10.1007\/s00417-002-0462-2"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_016","doi-asserted-by":"crossref","unstructured":"Volotinen, M, Turpeinen, M, Tolonen, A, Uusitalo, J, Maenpaa, J, Pelkonen, O. Timolol metabolism in human liver microsomes is mediated principally by CYP2D6. Drug Metab Dispos 2007;35:1135\u201341. https:\/\/doi.org\/10.1124\/dmd.106.012906.","DOI":"10.1124\/dmd.106.012906"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_017","doi-asserted-by":"crossref","unstructured":"Gaikovitch, EA, Cascorbi, I, Mrozikiewicz, PM, Brockm\u00f6ller, J, Fr\u00f6tschl, R, K\u00f6pke, K, et al.. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol 2003;59:303\u201312. https:\/\/doi.org\/10.1007\/s00228-003-0606-2.","DOI":"10.1007\/s00228-003-0606-2"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_018","doi-asserted-by":"crossref","unstructured":"Preskorn, SH, Kane, CP, Lobello, K, Nichols, AI, Fayyad, R, Buckley, G, et al.. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for Personalized Medicine. J Clin Psychiatr 2013;74:614\u201321. https:\/\/doi.org\/10.4088\/JCP.12m07807.","DOI":"10.4088\/JCP.12m07807"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_019","doi-asserted-by":"crossref","unstructured":"Petrovi\u0107, J, Pe\u0161i\u0107, V, Lauschke, VM. Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. Eur J Hum Genet 2020;1:88\u201394. https:\/\/doi.org\/10.1038\/s41431-019-0480-8.","DOI":"10.1038\/s41431-019-0480-8"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_020","doi-asserted-by":"crossref","unstructured":"Ikonnikova, AY, Filippova, MA, Surzhikov, SA, Pozhitnova, VO, Kazakov, RE, Lisitsa, TS, et al.. Biochip-based approach for comprehensive pharmacogenetic testing. Drug Metab Pers Ther 2020;36:33\u201340. https:\/\/doi.org\/10.1515\/dmpt-2020-0155.","DOI":"10.1515\/dmpt-2020-0155"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_021","doi-asserted-by":"crossref","unstructured":"Ju, S, Gao, Y, Cao, X, Zhang, XF, Yan, CC, Liu, FT. Association between the lower extremity deep venous thrombosis, the warfarin maintenance dose, and CYP2C9*3, CYP2D6*10, and CYP3A5*3 genetic polymorphisms: a case-control study. Genet Test Mol Biomarkers 2017;21:539\u201346. https:\/\/doi.org\/10.1089\/gtmb.2017.0090.","DOI":"10.1089\/gtmb.2017.0090"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_022","doi-asserted-by":"crossref","unstructured":"Yang, Y, Wu, K, Yuan, H, Yu, M. Cytochrome oxidase 2D6 gene polymorphism in primary open\u00a0\u2014 angle glaucoma with various effects to ophthalmic timolol. J Ocul Pharmacol Therapeut 2009;25:163\u201371. https:\/\/doi.org\/10.1089\/jop.2008.0028.","DOI":"10.1089\/jop.2008.0028"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_023","doi-asserted-by":"crossref","unstructured":"Yuan, H, Yu, M, Yang, Y, Wu, K, Lin, X, Li, J. Association of CYP2D6 single\u00a0\u2014 nucleotide polymorphism with response to ophthalmic timolol in primary open\u00a0\u2014 angle glaucoma\u00a0\u2014 a pilot study. J Ocul Pharmacol Therapeut 2010;26:497\u2013501. https:\/\/doi.org\/10.1089\/jop.2010.0013.","DOI":"10.1089\/jop.2010.0013"},{"key":"2025121207125697970_j_dmpt-2022-0117_ref_024","doi-asserted-by":"crossref","unstructured":"Nieminen, T, Lehtimaki, T, Maenpaa, J, Ropo, A, Uusitalo, H, K\u00e4h\u00f6nen, M. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest 2007;67:237\u201345. https:\/\/doi.org\/10.1080\/00365510601034736.","DOI":"10.1080\/00365510601034736"}],"container-title":["Drug Metabolism and Personalized Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dmpt-2022-0117\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dmpt-2022-0117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:00:15Z","timestamp":1765526415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dmpt-2022-0117\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,3,16]]},"published-print":{"date-parts":[[2023,6,5]]}},"alternative-id":["10.1515\/dmpt-2022-0117"],"URL":"https:\/\/doi.org\/10.1515\/dmpt-2022-0117","relation":{},"ISSN":["2363-8915"],"issn-type":[{"type":"electronic","value":"2363-8915"}],"subject":[],"published":{"date-parts":[[2022,8,24]]}}}