{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:09:59Z","timestamp":1778641799193,"version":"3.51.4"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Assistance Publique \u2013 H\u00f4pitaux de Paris","award":["CRC14111"],"award-info":[{"award-number":["CRC14111"]}]},{"name":"French Ministry of Health","award":["PHRC10_02-54"],"award-info":[{"award-number":["PHRC10_02-54"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cancer-associated thrombosis (CAT) is common and a leading cause of mortality in patients with cancer. In specific CAT scenarios, low-molecular-weight heparins (LMWHs), including tinzaparin, are preferred over direct oral anticoagulants. Despite the importance of understanding LMWH pharmacokinetics (PK) in cancer for optimizing CAT management, available data remain limited.<\/jats:p>\n                  <jats:p>To compare tinzaparin PK in cancer and non-cancer patients by developing a population PK model.<\/jats:p>\n                  <jats:p>This prospective, multicenter, case\u2013control trial enrolled patients receiving once-daily subcutaneous tinzaparin at a therapeutic dose of 175\u2009IU\u00b7kg\u22121, including matched cancer and non-cancer patients. Plasma anti-Xa activity was measured at multiple time points and analyzed using a non-linear mixed-effect modeling. A PK model was developed, and covariate effects were assessed for parameters of the model. The impact of cancer on tinzaparin PK was evaluated by incorporating cancer status as a categorical covariate.<\/jats:p>\n                  <jats:p>A total of 333 patients (including 46 matched cancer and non-cancer patients) were included in the analysis. A monocompartmental model with first-order absorption best described tinzaparin PK. The volume of distribution was associated with body weight, while clearance and anti-Xa activity were associated with creatinine clearance. No significant differences were observed between matched cancer and non-cancer patients in anti-Xa activity exposure at day 1 and steady state.<\/jats:p>\n                  <jats:p>PK profiles were comparable between cancer and non-cancer patients. Additionally, further studies should clarify the role of renal function in guiding tinzaparin dosing.<\/jats:p>","DOI":"10.1055\/a-2740-1841","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:20:10Z","timestamp":1764116410000},"source":"Crossref","is-referenced-by-count":1,"title":["Tinzaparin Pharmacokinetics in Patients with Cancer: A Comparative Modeling Study"],"prefix":"10.1055","clinical-trial-number":[{"clinical-trial-number":"nct02898051","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-0713","authenticated-orcid":false,"given":"Xavier","family":"Delavenne","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie et Toxicologie, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France"},{"name":"INSERM UMR1059 SAINBIOSE, Equipe Dysfonction Vasculaire et de l'H\u00e9mostase, Universit\u00e9 Jean-Monnet, Saint-Priest-en-Jarez, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7348-418X","authenticated-orcid":false,"given":"Jean","family":"Escal","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie et Toxicologie, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France"},{"name":"INSERM UMR1059 SAINBIOSE, Equipe Dysfonction Vasculaire et de l'H\u00e9mostase, Universit\u00e9 Jean-Monnet, Saint-Priest-en-Jarez, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Helley","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9matologie biologique, Assistance Publique H\u00f4pitaux de Paris-Centre Universit\u00e9 de Paris (APHP-CUP), H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France"},{"name":"INSERM UMR-S970 Paris Cardiovascular Research Centre, Team Endotheliopathy and Hemostasis Disorders, Paris Cit\u00e9 University, Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8214-3010","authenticated-orcid":false,"given":"Laurent","family":"Bertoletti","sequence":"additional","affiliation":[{"name":"INSERM UMR1059 SAINBIOSE, Equipe Dysfonction Vasculaire et de l'H\u00e9mostase, Universit\u00e9 Jean-Monnet, Saint-Priest-en-Jarez, France"},{"name":"Service de m\u00e9decine vasculaire et th\u00e9rapeutique, CHU Saint-Etienne, Saint-Priest-en-Jarez, France"},{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"INSERM CIC 1408, CHU de Saint-\u00c9tienne, Saint-Priest-en-Jarez, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Falvo","sequence":"additional","affiliation":[{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"Department of Vascular Pathology, Centre Hospitalier Universitaire Dijon-Bourgogne, Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-7880","authenticated-orcid":false,"given":"Isabelle","family":"Mah\u00e9","sequence":"additional","affiliation":[{"name":"INSERM UMR-S970 Paris Cardiovascular Research Centre, Team Endotheliopathy and Hemostasis Disorders, Paris Cit\u00e9 University, Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"Service de M\u00e9decine Interne, H\u00f4pital Louis Mourier, Assistance Publique-H\u00f4pitaux de Paris, Colombes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Crichi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saint-Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Couturaud","sequence":"additional","affiliation":[{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"INSERM Unit\u00e9 1304 Groupe d'\u00c9tude de la Thrombose de Bretagne Occidentale, Brest, France"},{"name":"INSERM Unit\u00e9 1412 centre d'Investigation Clinique Universitaire de Brest, Brest, France"},{"name":"D\u00e9partement de M\u00e9decine Interne et Pneumologie, CHU Brest, Brest, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Antoinette","family":"Sevestre","sequence":"additional","affiliation":[{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"Service de M\u00e9decine Vasculaire, EA Chim\u00e8re 7516, CHU d'Amiens-Picardie, Amiens, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Pavic","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Qu\u00e9bec, Canada"},{"name":"Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laetitia","family":"Mauge","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9matologie biologique, Assistance Publique H\u00f4pitaux de Paris-Centre Universit\u00e9 de Paris (APHP-CUP), H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France"},{"name":"INSERM UMR-S970 Paris Cardiovascular Research Centre, Team Endotheliopathy and Hemostasis Disorders, Paris Cit\u00e9 University, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Zia-Chahabi","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9matologie biologique, Assistance Publique H\u00f4pitaux de Paris-Centre Universit\u00e9 de Paris (APHP-CUP), H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Vilfaillot","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital europ\u00e9en Georges-Pompidou, Unit\u00e9 de Recherche Clinique, APHP. Centre, Paris, France"},{"name":"INSERM, Centre d'Investigation Clinique 1418 (CIC1418) \u00c9pid\u00e9miologie Clinique, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliette","family":"Djadi-Prat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Service de Pneumologie et de Soins Intensifs, AP-HP, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Mismetti","sequence":"additional","affiliation":[{"name":"INSERM UMR1059 SAINBIOSE, Equipe Dysfonction Vasculaire et de l'H\u00e9mostase, Universit\u00e9 Jean-Monnet, Saint-Priest-en-Jarez, France"},{"name":"Service de m\u00e9decine vasculaire et th\u00e9rapeutique, CHU Saint-Etienne, Saint-Priest-en-Jarez, France"},{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"INSERM CIC 1408, CHU de Saint-\u00c9tienne, Saint-Priest-en-Jarez, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Meyer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Sanchez","sequence":"additional","affiliation":[{"name":"INSERM UMR-S970 Paris Cardiovascular Research Centre, Team Endotheliopathy and Hemostasis Disorders, Paris Cit\u00e9 University, Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"Investigation Network on Venous Thrombo-Embolism-French Clinical Research Infrastructure Network, Saint-\u00c9tienne, France"},{"name":"Service de Pneumologie et de Soins Intensifs, AP-HP, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"10","key":"ref1","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1182\/blood-2013-04-460121","article-title":"Epidemiology of cancer-associated venous thrombosis","volume":"122","author":"J F Timp","year":"2013","journal-title":"Blood"},{"issue":"08","key":"ref2","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41568-024-00708-4","article-title":"Why do patients with cancer die?","volume":"24","author":"A Boire","year":"2024","journal-title":"Nat Rev Cancer"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"101348","DOI":"10.1016\/j.beha.2022.101348","article-title":"A review of latest clinical practice guidelines for the management of cancer-associated thrombosis","volume":"35","author":"C Frere","year":"2022","journal-title":"Best Pract Res Clin Haematol"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13045-022-01289-1","article-title":"Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials","volume":"15","author":"C Frere","year":"2022","journal-title":"J Hematol Oncol"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.acvd.2023.11.009","article-title":"Management of cancer-associated thromboembolism in vulnerable population","volume":"117","author":"S Laporte","year":"2024","journal-title":"Arch Cardiovasc Dis"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.acvd.2023.11.010","article-title":"Anticoagulant treatment of cancer-associated thromboembolism","volume":"117","author":"I Mah\u00e9","year":"2024","journal-title":"Arch Cardiovasc 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No","volume":"2","author":"H Bounameaux","year":"2004","journal-title":"J Thromb Haemost"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2740-1841.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:20:16Z","timestamp":1764116416000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2740-1841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":36,"URL":"https:\/\/doi.org\/10.1055\/a-2740-1841","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]}}}