{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:37:15Z","timestamp":1788172635888,"version":"build-2803163510"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31702296"],"award-info":[{"award-number":["31702296"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31672599"],"award-info":[{"award-number":["31672599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31402246"],"award-info":[{"award-number":["31402246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Retapamulin, a semisynthetic pleuromutilin derivative, is exclusively used for the topical short-term medication of impetigo and staphylococcal infections. In the present study, we report that retapamulin is adequately and rapidly metabolized\n            <jats:italic>in vitro<\/jats:italic>\n            via various metabolic pathways, such as hydroxylation, including mono-, di-, and trihydroxylation, and demethylation. Like tiamulin and valnemulin, the major metabolic routes of retapamulin were hydroxylation at the 2\u03b2 and 8\u03b1 positions of the mutilin moiety. Moreover,\n            <jats:italic>in vivo<\/jats:italic>\n            metabolism concurred with the results of the\n            <jats:italic>in vitro<\/jats:italic>\n            assays. Additionally, we observed significant interspecies differences in the metabolism of retapamulin. Until now, modifying the side chain was the mainstream method for new drug discovery of the pleuromutilins. This approach, however, could not resolve the low bioavailability and short efficacy of the drugs. Considering the rapid metabolism of the pleuromutilins mediated by cytochrome P450 enzymes, we propose that blocking the active metabolic site (C-2 and C-8 motif) or administering the drug in combination with cytochrome P450 enzyme inhibitors is a promising pathway in the development of novel pleuromutilin drugs with slow metabolism and long efficacy.\n          <\/jats:p>","DOI":"10.1128\/aac.02388-17","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T11:30:46Z","timestamp":1516620646000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Unraveling the Metabolic Routes of Retapamulin: Insights into Drug Development of Pleuromutilins"],"prefix":"10.1128","volume":"62","author":[{"given":"Feifei","family":"Sun","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China"},{"name":"Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China"},{"name":"Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard Bryan","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Yantai University, Yantai, Shandong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Laboratory of Risk Assessment for Quality and Safety of Bee Products, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.12.6212-6213.2005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.05.022"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3345\/kjp.2017.60.5.151"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.2.244-269.2001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/76.2.246"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.00681"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2573-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1975.tb03976.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03721.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02595.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.10.127"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.10.123"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2010.01.058"},{"key":"e_1_3_3_15_2","first-page":"760","article-title":"Tiamulin activity against Brachyspira hyodysenteriae","volume":"163","author":"Burch DG","year":"2008","unstructured":"Burch DG. 2008. Tiamulin activity against Brachyspira hyodysenteriae. Vet Rec 163:760.","journal-title":"Vet Rec"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5288(97)90010-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1053\/jinf.2001.0910"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00297-X"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.2.6.591"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm8000136"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.05.011"},{"key":"e_1_3_3_22_2","volume-title":"Valnemulin","author":"European Agency for the Evaluation of Medicinal Products","year":"1998","unstructured":"European Agency for the Evaluation of Medicinal Products. 1998. Committee for Veterinary Medicinal Products. Valnemulin. Summary report, 339\u2013398. European Agency for the Evaluation of Medicinal Products, London, United Kingdom. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Maximum_Residue_Limits_-_Report\/2009\/11\/WC500015381.pdf."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12389"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.6b04377"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf5012402"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2006.03.023"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00282-13"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2017.1257115"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700043"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2014-0081"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01784-16"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02582-16"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00066-17"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00015-15"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2017.06.002"},{"key":"e_1_3_3_36_2","first-page":"71","article-title":"Current status of the industrial manufacture of soft drugs by factories of the Soiuzlikzasoby All-Union Manufacturing Association","volume":"1980","author":"Rassokha TM","year":"1980","unstructured":"Rassokha TM, Kabachna AV, Pertsev IM. 1980. Current status of the industrial manufacture of soft drugs by factories of the Soiuzlikzasoby All-Union Manufacturing Association. Farm Zh 1980:71. (In Ukrainian.)","journal-title":"Farm Zh"},{"key":"e_1_3_3_37_2","first-page":"599","article-title":"Prodrugs and soft drugs","volume":"58","author":"Stanczak A","year":"2006","unstructured":"Stanczak A, Ferra A. 2006. Prodrugs and soft drugs. Pharmacol Rep 58:599\u2013613.","journal-title":"Pharmacol Rep"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.1994.10.3"},{"key":"e_1_3_3_39_2","first-page":"7","article-title":"FDA approves 2 new protease inhibitors: ritonavir (Norvir) and Crixivan (indinavir sulfate). Food and Drug Administration","volume":"8","author":"Schouten JT","year":"1996","unstructured":"Schouten JT. 1996. FDA approves 2 new protease inhibitors: ritonavir (Norvir) and Crixivan (indinavir sulfate). Food and Drug Administration. STEP Perspect 8:7\u20138.","journal-title":"STEP Perspect"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02388-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02388-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:09:42Z","timestamp":1645477782000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02388-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1128\/AAC.02388-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.02388-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02388-17"}}