{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T17:20:50Z","timestamp":1783358450630,"version":"3.54.6"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Tandospirone citrate (TDS) is commonly used for the treatment of patients with generalized anxiety disorder in clinical practice, and several studies are developing new indications for TDS. However, the <jats:italic>in vivo<\/jats:italic> processes and absorption properties of TDS have not been systematically investigated. In this work, we conducted a comprehensive investigation using <jats:italic>in vivo<\/jats:italic>, <jats:italic>in vitro<\/jats:italic>, and <jats:italic>ex vivo<\/jats:italic> approaches, involving animal and cellular models, to examine the pharmacokinetic properties and absorption mechanisms of TDS. The results of <jats:italic>in vivo<\/jats:italic> studies revealed that the half-life (<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>) of TDS was 1.380 \u00b1 0.46\u00a0h and 1.224 \u00b1 0.39\u00a0h following intragastric (i.g.) and intravenous (i.v.) administration of 20\u00a0mg\/kg TDS, respectively. This indicates that TDS is rapidly eliminated in rats. The area under the curve (AUC) of TDS after i.g. and i.v. administration was 114.7 \u00b1 40\u00a0ng\/mL*h and 48,400 \u00b1 19,110\u00a0ng\/mL*h, respectively, and the absolute bioavailability of TDS was found to be low (0.24%). Furthermore, TDS was extensively metabolized in rats, with the AUC of the major active metabolite [1-[2-pyrimidyl]-piperazine] being approximately 16.38-fold higher than that of TDS after i.g. administration. The results from the <jats:italic>in vitro<\/jats:italic> Caco-2 cell model and <jats:italic>ex vivo<\/jats:italic> everted gut sac experiment demonstrated that TDS exhibited good permeability, and its transport was influenced by concentration, temperature, and pH. Passive diffusion was identified as the main absorption mechanism. In conclusion, TDS is classified as a Biopharmaceutics Classification System (BCS) class I drug, characterized by high solubility and permeability. The low absolute bioavailability of TDS may be attributed to its rapid metabolism. The pharmacokinetic data and absorption characteristics obtained in this study provide fundamental information for the further development and utilization of TDS.<\/jats:p>","DOI":"10.3389\/fphar.2023.1283103","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T10:14:54Z","timestamp":1699265694000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics and absorption mechanism of tandospirone citrate"],"prefix":"10.3389","volume":"14","author":[{"given":"Rong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/j.2042-7158.2011.01391.x","article-title":"Everted gut sac model as a tool in pharmaceutical research: limitations and applications","volume":"64","author":"Alam","year":"2012","journal-title":"J. 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