{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:34:40Z","timestamp":1787589280102,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jagiellonian University Medical College, Krak\u00f3w","award":["K\/ZDS\/006119"],"award-info":[{"award-number":["K\/ZDS\/006119"]}]},{"name":"Jagiellonian University Medical College, Krak\u00f3w","award":["K\/ZDS\/007070"],"award-info":[{"award-number":["K\/ZDS\/007070"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objective: The aim of this study was to develop quantitative structure\u2013pharmacokinetics relationship (QSPKR) models for a group of xanthine derivatives with proven pharmacological activity and to investigate its applicability for the prediction of the pharmacokinetics of these compounds. Methods: The SYBYL-X, KowWin, and MarvinSketch programs were employed to generate a total of fourteen descriptor variables for a series of new compounds: 7- and 7,8-substituted theophylline derivatives (GR-1\u2013GR-8) and three well-known methylxanthines. Pharmacokinetic profiles of all compounds were determined after intravenous administration of studied compounds to cannulated male rats. Pharmacokinetic parameters were calculated using noncompartmental analysis. Results: Multiple linear regression revealed that logD was the main determinant of the variability in Vss, \u03bbz, and CL of the studied compounds. Moreover, \u03bbz and CL depended on LUMO and HEFO, while for Vz COAR was the only explanatory variable. The developed QSPKR models accounted for most of the variation in Vss, \u03bbz, CL, and fraction unbound (fu) (R2 ranged from 0.68 to 0.91). Cross-validation confirmed the predictive ability of the models (Q2 = 0.60, 0.71, 0.34, and 0.32 for Vss, \u03bbz, CL, and fu, respectively). Conclusions: The multivariate QSPKR models developed in this study adequately predicted the overall pharmacokinetic behavior of xanthine derivatives in rats.<\/jats:p>","DOI":"10.3390\/pharmaceutics16111463","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T05:36:45Z","timestamp":1731908205000},"page":"1463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics and Quantitative Structure\u2013Pharmacokinetics Relationship Study of Xanthine Derivatives with Antidepressant, Anti-Inflammatory, and Analgesic Activity in Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-9709","authenticated-orcid":false,"given":"Artur","family":"\u015awierczek","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Szafarz","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1743-350X","authenticated-orcid":false,"given":"Agnieszka","family":"Cios","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3223-0014","authenticated-orcid":false,"given":"Jan","family":"Kobierski","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1186-3085","authenticated-orcid":false,"given":"Krzysztof","family":"Pociecha","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4514-6578","authenticated-orcid":false,"given":"Daniel","family":"Attard Saliba","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Ch\u0142o\u0144-Rzepa","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Wyska","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.addr.2006.08.002","article-title":"Quantitative Structure\u2013Pharmacokinetic\/Pharmacodynamic Relationships","volume":"58","author":"Mager","year":"2006","journal-title":"Adv. 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