{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:03:08Z","timestamp":1790877788603,"version":"4.1.0"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFA1301200"],"award-info":[{"award-number":["2021YFA1301200"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373961"],"award-info":[{"award-number":["82373961"]}],"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":["82073945"],"award-info":[{"award-number":["82073945"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the scientific research project of Furong laboratory of Central South University","award":["2023SK2083"],"award-info":[{"award-number":["2023SK2083"]}],"id":[{"id":"https:\/\/ror.org\/00f1zfq44","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2022JJ30949"],"award-info":[{"award-number":["2022JJ30949"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Ticagrelor, a commonly used antiplatelet medication, has been found to exhibit considerable inter-individual pharmacodynamic variability. Recent studies have revealed a close relationship between pharmacokinetics and pharmacodynamics, both of which can be influenced by gut microbiota. In this study, we explored whether the pharmacokinetics of ticagrelor is mediated by intestinal flora. We enrolled 22 healthy participants to assess the clinical pharmacokinetic profiles of ticagrelor and its metabolite AR-C124910XX after a single oral dose of ticagrelor. The fecal microbial compositions of individuals who exhibited distinct pharmacokinetic parameters were analyzed using 16S rRNA gene sequencing. Additionally, we conducted experiments involving the co-incubation of ticagrelor with fecal bacteria and a systematic exploration of the pharmacokinetics of ticagrelor in pseudo-germ-free (PGF) rats to illustrate the role of gut microbiota in ticagrelor metabolism, both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Our findings revealed a three-fold difference in the bioavailability of ticagrelor among individuals. However, no difference was found in the composition of gut microbiota among individuals with different pharmacokinetic parameters. Quantitative analysis showed that gut microbiota cannot directly metabolize ticagrelor. Furthermore, there were no significant differences in AUC\n                    <jats:sub>(0\u201348)<\/jats:sub>\n                    , AUC\n                    <jats:sub>(0-\u221e),<\/jats:sub>\n                    and C\n                    <jats:sub>max<\/jats:sub>\n                    between ticagrelor and AR-C124910XX in PGF rats compared to normal control, either by single intragastric or intravenous administration. In conclusion, these findings suggest that gut microbiota has no impact on the pharmacokinetics of ticagrelor.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359660","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:25:23Z","timestamp":1790875523000},"page":"e0359660","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ticagrelor and gut microbiota: Absence of pharmacokinetic interaction in vitro and in vivo studies"],"prefix":"10.1371","volume":"21","author":[{"given":"Pan","family":"Qu","sequence":"first","affiliation":[{"name":"Xiangya Hospital, Central South University","place":["Changsha, China"],"department":["Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical Pharmacology"]},{"name":"Hunan Prevention and Treatment Institute for Occupational Diseases, Affiliated Prevention and Treatment Institute for Occupational Diseases of University of South China","place":["Changsha, China"],"department":["Department of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Gao","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University","place":["Changsha, China"],"department":["Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical Pharmacology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University","place":["Changsha, China"],"department":["Department of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tang","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University","place":["Changsha, China"],"department":["Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical Pharmacology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University","place":["Changsha, China"],"department":["Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical 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