{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:15Z","timestamp":1787017035877,"version":"build-2736575974"},"reference-count":28,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["5K23AR075874"],"award-info":[{"award-number":["5K23AR075874"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2024,4,20]]},"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For patients receiving HCQ 400\u2009mg daily, simulated random blood levels &lt;200\u2009ng\/mL were exceedingly uncommon in fully adherent patients (&lt;0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were &lt;200\u2009ng\/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to &lt;200\u2009ng\/mL after 2\u20134\u2009days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2023-001090","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T13:35:12Z","timestamp":1714484112000},"page":"e001090","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Interpreting hydroxychloroquine blood levels for medication non-adherence: a pharmacokinetic study"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-1680","authenticated-orcid":false,"given":"Stephen","family":"Balevic","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"},{"name":"Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-2932","authenticated-orcid":false,"given":"Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-8642","authenticated-orcid":false,"given":"Jennifer L","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-5545","authenticated-orcid":false,"given":"Amanda","family":"Eudy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, Durham, North Carolina, 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