{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:42:55Z","timestamp":1761057775429},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,6,6]],"date-time":"2003-06-06T00:00:00Z","timestamp":1054857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm & Drug Disp"],"published-print":{"date-parts":[[2003,9]]},"abstract":"Abstract<\/jats:title>Background<\/jats:italic>\u2014The objective of this study was to investigate whether the use of a depot formulation would enhance the antithrombotic effect of the direct thrombin inhibitor melagatran.<\/jats:p>Methods and Results<\/jats:italic>\u2014In a rat venous thrombosis model, animals were openly randomized to receive subcutaneously (s.c.) either vehicle (saline, cyclodextrin or poloxamer) or melagatran (0.5 \u00b5;mol\/kg) dissolved in vehicle. An additional injection of cyclodextrin or poloxamer was given at another site to investigate whether the vehicle itself had any additional effect. All injections were given 30 min before induction of thrombus formation. Thrombus formation was induced by ferric chloride, together with stenosis of the caval vein, during a short period of inhalation anaesthesia. Five hours later the thrombi were harvested and their wet weight determined. Thrombus size was comparable across the vehicle\u2010only groups. The antithrombotic effects of melagatran in saline or poloxamer were comparable while melagatran in cyclodextrin was less effective. The effects of melagatran in saline, cyclodextrin or poloxamer were not enhanced by additional cyclodextrin or poloxamer. Thrombin time (TT) and activated partial thromboplastin time (aPTT) at the end of the experiment were prolonged to a greater extent in the groups receiving melagatran in cyclodextrin or poloxamer compared with those receiving melagatran in saline.<\/jats:p>Conclusion<\/jats:italic>\u2014In this vena cava thrombosis model, no enhanced antithrombotic effect was observed with melagatran given as a s.c. depot formulation in cyclodextrin or poloxamer compared with that in saline. Copyright \u00a9 2003 John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.363","type":"journal-article","created":{"date-parts":[[2003,9,9]],"date-time":"2003-09-09T13:24:10Z","timestamp":1063113850000},"page":"251-257","source":"Crossref","is-referenced-by-count":3,"title":["Three vehicle formulations for melagatran, a direct thrombin inhibitor, evaluated in a vena cava thrombosis model in the rat"],"prefix":"10.1002","volume":"24","author":[{"given":"Margareta","family":"Elg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inger","family":"B\u00f6rjesson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Carlsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,6,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614245"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1055\/s-0038-1665419","article-title":"Antithrombotic effects of two low molecular weight thrombin inhibitors and a low\u2010molecular weight heparin in a caval vein thrombosis model in the rat","volume":"78","author":"Eriksson BI","year":"1997","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(02)00257-8"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1055\/s-0038-1657729","article-title":"The importance of enzyme inhibition kinetics for the effect of thrombin inhibitors in a rat model of arterial thrombosis","volume":"78","author":"Elg M","year":"1997","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(98)00213-8"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199803000-00003"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614477"},{"key":"e_1_2_1_9_2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1055\/s-0037-1612978","article-title":"A dose\u2010ranging study of the oral direct thrombin inhibitor, ximelagatran, and its subcutaneous form, melagatran, compared with dalteparin in the prophylaxis of venous thromboembolism after total hip or total knee replacement: METHRO I","volume":"87","author":"Eriksson BI","year":"2002","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012136608249"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(01)00429-7"}],"container-title":["Biopharmaceutics & Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdd.363","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T21:43:57Z","timestamp":1700171037000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,6]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1002\/bdd.363"],"URL":"https:\/\/doi.org\/10.1002\/bdd.363","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"value":"0142-2782","type":"print"},{"value":"1099-081X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,6]]}}}