{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T05:30:01Z","timestamp":1738128601788,"version":"3.33.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204703","82304847"],"award-info":[{"award-number":["82204703","82304847"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Hydroxychloroquine (HCQ) is recommended for the long\u2010term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long\u2010term administration is unknown. This study aimed to establish a population pharmacokinetic model for long\u2010term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 274 HCQ whole\u2010blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6\u00a0months, with a median duration of 36\u2009months. A nonlinear mixed\u2010effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The final model describing the HCQ blood concentration\u2013time profile was a compartmental model with first\u2010order absorption. The estimated values for apparent clearance and volume of distribution were 16.4\u00a0L\/h and 1220\u2009L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5\u00a0mg\/kg was appropriate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We developed a population pharmacokinetic model for long\u2010term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16257","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T08:34:23Z","timestamp":1727166863000},"page":"365-373","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetics of long\u2010term hydroxychloroquine therapy in patients with rheumatic diseases"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-2105","authenticated-orcid":false,"given":"Chunlan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University Anhui Medical University  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiyun","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Affiliated Psychological Hospital of Anhui Medical 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