{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:17:45Z","timestamp":1772727465128,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18\/151"],"award-info":[{"award-number":["18\/151"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011209","name":"Australian and New Zealand Society for Geriatric Medicine","doi-asserted-by":"publisher","award":["R295"],"award-info":[{"award-number":["R295"]}],"id":[{"id":"10.13039\/100011209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1007\/s40262-025-01551-y","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:22:25Z","timestamp":1753712545000},"page":"1517-1529","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Influence of Patient Factors on the Population Pharmacokinetics of Colchicine: Implications for Safe and Effective Dosing"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9313-9252","authenticated-orcid":false,"given":"Daniel F. B.","family":"Wright","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-2766","authenticated-orcid":false,"given":"Hailemichael Z.","family":"Hishe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-4476","authenticated-orcid":false,"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Horne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Drake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Haslett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0138-2912","authenticated-orcid":false,"given":"Lisa K.","family":"Stamp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"issue":"6","key":"1551_CR1","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1002\/art.41247","volume":"72","author":"JD FitzGerald","year":"2020","unstructured":"FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, Gelber AC, Harrold LR, Khanna D, King C, Levy G. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Rheumatol. 2020;72(6):879\u201395.","journal-title":"Arthritis Rheumatol"},{"issue":"7","key":"1551_CR2","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.jacc.2023.05.055","volume":"82","author":"K Nelson","year":"2023","unstructured":"Nelson K, Fuster V, Ridker PM. Low-dose colchicine for secondary prevention of coronary artery disease: JACC review topic of the week. J Am Coll Cardiol. 2023;82(7):648\u201360.","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"1551_CR3","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1002\/art.27327","volume":"62","author":"RA Terkeltaub","year":"2010","unstructured":"Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: twenty-four\u2013hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheumatol. 2010;62(4):1060\u20138.","journal-title":"Arthritis Rheumatol"},{"issue":"3","key":"1551_CR4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0049-0172(91)90003-I","volume":"21","author":"C Putterman","year":"1991","unstructured":"Putterman C, Ben-Chetrit E, Caraco Y, Levy M. Colchicine intoxication: clinical pharmacology, risk factors, features, and management. Semin Arthritis Rheum. 1991;21(3):143\u201355.","journal-title":"Semin Arthritis Rheum"},{"key":"1551_CR5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/BF00609430","volume":"37","author":"G Thomas","year":"1989","unstructured":"Thomas G, Girre C, Scherrmann JM, Francheteau P, Steimer JL. Zero-order absorption and linear disposition of oral colchicine in healthy volunteers. Euro J Clin Pharmacol. 1989;37:79\u201384.","journal-title":"Euro J Clin Pharmacol."},{"key":"1551_CR6","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/BF03190118","volume":"14","author":"G Achtert","year":"1989","unstructured":"Achtert G, Scherrmann JM, Christen MO. Pharmacokinetics\/bioavailability of colchicine in healthy male volunteers. Eur J Drug Metab Pharmacokinet. 1989;14:317\u201322.","journal-title":"Eur J Drug Metab Pharmacokinet"},{"issue":"10","key":"1551_CR7","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1002\/j.1552-4604.1996.tb04753.x","volume":"36","author":"GM Ferron","year":"1996","unstructured":"Ferron GM, Rochdi M, Jusko WJ, Scherrmann JM. Oral absorption characteristics and pharmacokinetics of colchicine in healthy volunteers after single and multiple doses. J Clin Pharmacol. 1996;36(10):874\u201383.","journal-title":"J Clin Pharmacol"},{"issue":"5","key":"1551_CR8","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1111\/j.1472-8206.1989.tb00688.x","volume":"3","author":"C Girre","year":"1989","unstructured":"Girre C, Thomas G, Scherrmann JM, Crouzette J, Fournier PE. Model-independent pharmacokinetics of colchicine after oral administration to healthy volunteers. Fundam Clin Pharmacol. 1989;3(5):537\u201343.","journal-title":"Fundam Clin Pharmacol"},{"key":"1551_CR9","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/BF00194404","volume":"46","author":"M Rochdi","year":"1994","unstructured":"Rochdi M, Sabouraud A, Girre C, Venet R, Scherrmann JM. Pharmacokinetics and absolute bioavailability of colchicine after iv and oral administration in healthy human volunteers and elderly subjects. Euro J Clin Pharmacol. 1994;46:351\u20134.","journal-title":"Euro J Clin Pharmacol."},{"issue":"4","key":"1551_CR10","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/0002-9343(70)90043-4","volume":"48","author":"SL Wallace","year":"1970","unstructured":"Wallace SL, Omokoku B, Ertel NH. Colchicine plasma levels: implications as to pharmacology and mechanism of action. Am J Med. 1970;48(4):443\u20138.","journal-title":"Am J Med"},{"key":"1551_CR11","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s12325-012-0028-6","volume":"29","author":"S Wason","year":"2012","unstructured":"Wason S, Faulkner RD, Davis MW. Are dosing adjustments required for colchicine in the elderly compared with younger patients? Adv Ther. 2012;29:551\u201361.","journal-title":"Adv Ther"},{"key":"1551_CR12","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1007\/s40261-014-0238-6","volume":"34","author":"S Wason","year":"2014","unstructured":"Wason S, Mount D, Faulkner R. Single-dose, open-label study of the differences in pharmacokinetics of colchicine in subjects with renal impairment, including end-stage renal disease. Clin Drug Investig. 2014;34:845\u201355.","journal-title":"Clin Drug Investig"},{"issue":"4","key":"1551_CR13","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1177\/039463201202500429","volume":"25","author":"Y Berkun","year":"2012","unstructured":"Berkun Y, Wason S, Brik R, Butbul Y, Ben-Chetrit E, Hashkes PJ, Livneh A, Ozen S, Ozdogan H, Faulkner R, Davis MW. Pharmacokinetics and Colchicine in Pediatric and Adult Patients with Familial Mediterranean Fever. Int J Immunopathol Pharmacol. 2012;25(4):1121\u201330.","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"2","key":"1551_CR14","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/art.1780250219","volume":"25","author":"E Zylber Katz","year":"1982","unstructured":"Zylber Katz E, Ehrenfeld M, Levy M, Eliakim M. Plasma colchicine concentration in patients with recurrent polyserositis (familial mediterranean fever) on long-term prophylaxis. Arthritis Rheumatol. 1982;25(2):227\u201331.","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"1551_CR15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0006-2952(96)00693-4","volume":"53","author":"T Tateishi","year":"1997","unstructured":"Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ. Colchicine biotransformation by human liver microsomes: identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol. 1997;53(1):111\u20136.","journal-title":"Biochem Pharmacol"},{"issue":"9","key":"1551_CR16","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3109\/0886022X.2011.605980","volume":"33","author":"F Ozen","year":"2011","unstructured":"Ozen F, Silan C, Uludag A, Candan F, Silan F, Ozdemir S, Atik S, Ozdemir O. Association between ABCB1 (MDR1) gene 3435 C> T polymorphism and colchicine unresponsiveness of FMF patients. Ren Fail. 2011;33(9):899\u2013903.","journal-title":"Ren Fail"},{"issue":"5","key":"1551_CR17","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/0026-0495(73)90247-3","volume":"22","author":"SL Wallace","year":"1973","unstructured":"Wallace SL, Ertel NH. Plasma levels of colchicine after oral administration of a single dose. Metabolism. 1973;22(5):749\u201353.","journal-title":"Metabolism"},{"issue":"1","key":"1551_CR18","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.amjmed.2021.07.025","volume":"135","author":"PC Robinson","year":"2022","unstructured":"Robinson PC, Terkeltaub R, Pillinger MH, Shah B, Karalis V, Karatza E, Liew D, Imazio M, Cornel JH, Thompson PL, Nidorf M. Consensus statement regarding the efficacy and safety of long-term low-dose colchicine in gout and cardiovascular disease. Am J Med. 2022;135(1):32\u20138.","journal-title":"Am J Med"},{"issue":"3","key":"1551_CR19","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1007\/s11926-002-0073-2","volume":"4","author":"Y Molad","year":"2002","unstructured":"Molad Y. Update on colchicine and its mechanism of action. Curr Rheumat Rep. 2002;4(3):252\u20136.","journal-title":"Curr Rheumat Rep."},{"issue":"12","key":"1551_CR20","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1136\/ard-2023-224731","volume":"82","author":"L Stamp","year":"2023","unstructured":"Stamp L, Horne A, Mihov B, Drake J, Haslett J, Chapman PT, Frampton C, Dalbeth N. Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial. Ann Rheum Dis. 2023;82(12):1626\u201334.","journal-title":"Ann Rheum Dis"},{"key":"1551_CR21","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s10928-008-9094-4","volume":"35","author":"JE Ahn","year":"2008","unstructured":"Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to handling data below the quantification limit using NONMEM VI. J Pharmacokinet Pharmacodyn. 2008;35:401\u201321.","journal-title":"J Pharmacokinet Pharmacodyn"},{"issue":"6","key":"1551_CR22","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1080\/00498254.2021.1909782","volume":"51","author":"E Karatza","year":"2021","unstructured":"Karatza E, Ismailos G, Karalis V. Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens. Xenobiotica. 2021;51(6):643\u201356.","journal-title":"Xenobiotica"},{"issue":"10","key":"1551_CR23","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.2165\/00003088-200544100-00004","volume":"44","author":"S Janmahasatian","year":"2005","unstructured":"Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051\u201365.","journal-title":"Clin Pharmacokinet"},{"issue":"1","key":"1551_CR24","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2133\/dmpk.24.25","volume":"24","author":"BJ Anderson","year":"2009","unstructured":"Anderson BJ, Holford NHG. Mechanistic basis of using body size and maturation to predict clearance in humans. Drug Metab Pharmacokinet. 2009;24(1):25\u201336.","journal-title":"Drug Metab Pharmacokinet"},{"key":"1551_CR25","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1146\/annurev.pharmtox.48.113006.094708","volume":"48","author":"BJ Anderson","year":"2008","unstructured":"Anderson BJ, Holford NHG. Mechanism-based concepts of size and maturity in pharmacokinetics. Ann Rev Pharmacol Toxicol. 2008;48:303\u201332.","journal-title":"Ann Rev Pharmacol Toxicol."},{"issue":"1","key":"1551_CR26","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1159\/000180580","volume":"16","author":"DW Cockcroft","year":"1976","unstructured":"Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31\u201341.","journal-title":"Nephron"},{"key":"1551_CR27","unstructured":"Flockhart DA, Thacker, D., McDonald, C., Desta, Z. The Flockhart Cytochrome P450 Drug-Drug Interaction Table. Division of Clinical Pharmacology, Indiana University School of Medicine (Updated 2021). https:\/\/drug-interactions.medicine.iu.edu\/. Accessed 27 Jan 2024."},{"key":"1551_CR28","unstructured":"UpToDate. Inhibitors and inducers of P-glycoprotein (P-gp) drug efflux pump (P-gp multidrug resistance transporter) https:\/\/www.uptodate.com\/contents\/image?imageKey=EM\/73326. Accessed 27 Jan 2024."},{"key":"1551_CR29","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1007\/s10928-016-9487-8","volume":"43","author":"AG Dosne","year":"2016","unstructured":"Dosne AG, Bergstrand M, Harling K, Karlsson MO. Improving the estimation of parameter uncertainty distributions in nonlinear mixed effects models using sampling importance resampling. J Pharmacokinet Pharmacodyn. 2016;43:583\u201396.","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"1551_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/eurheartj\/ehaf174","volume":"00","author":"M Samuel","year":"2025","unstructured":"Samuel M, Berry C, Dub\u00e9 MP, Koenig W, L\u00f3pez-Send\u00f3n J, Maggioni AP, Pinto FJ, Roubille F, Tardif JC. Long-term trials of colchicine for secondary prevention of vascular events: a meta-analysis. Eur Heart J. 2025;00:1\u201312. https:\/\/doi.org\/10.1093\/eurheartj\/ehaf174.","journal-title":"Eur Heart J"},{"key":"1551_CR31","doi-asserted-by":"crossref","unstructured":"Katz EZ, Ehrenfeld M, Levy M, Eliakim M. Plasma colchicine concentration in patients with recurrent polyserositis (familial Mediterranean fever) on long-term prophylaxis. Arthritis Rheum [Internet]. 1982;25(2):227\u201331.","DOI":"10.1002\/art.1780250219"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01551-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-025-01551-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01551-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:49:05Z","timestamp":1759146545000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-025-01551-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":31,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["1551"],"URL":"https:\/\/doi.org\/10.1007\/s40262-025-01551-y","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]},"assertion":[{"value":"10 July 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The data used were generated from studies funded by the Health Research Council of New Zealand (18\/151) and Arthritis New Zealand (R295).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Nicola Dalbeth has received consulting fees, speaker fees or grants from Novartis, Horizon, Selecta, Arthrosi, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, Dexcel Pharma, Shanton Pharma, Sobi, Avalo, Biomarin, Crystalys and Medcryst outside the submitted work. Lisa Stamp has received funding from the Health Research Council of New Zealand and Arthritis New Zealand related to the current work; royalties from Up-to-Date. The other authors report no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Analysed data may be made available to external collaborators upon reasonable request following review by the authors and with appropriate ethical approvals and acknowledgements.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"The study received ethical approval from the New Zealand Health and Disability Ethics Committee (18\/STH\/156). The authors confirm that the study was performed in accordance with the ethical standards laid out in the 1964 Declaration of Helsinki and its later amendments.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Participants provided written informed consent.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The code used for modelling and simulation is provided as a supplement to this paper.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"The colchicine clinical trial that generated the data was designed and led by LS and ND. Data collection was conducted by AH, JH and JD. DW conceptualised and designed the modelling analysis. DW and HH conducted the data analysis. DW drafted the manuscript. LS, ND, HH, AH, JH and JD edited and approved drafts of the manuscript. All authors read and approved the final version of this manuscript.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}