{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:27:26Z","timestamp":1747801646385},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T00:00:00Z","timestamp":1145577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To develop an appropriate dosing strategy for continuous intravenous infusions (CII) of enoxaparin by minimizing the percentage of steady\u2010state anti\u2010Xa concentration (<jats:italic>C<\/jats:italic><jats:sub>ss<\/jats:sub>) outside the therapeutic range of 0.5\u20131.2\u2003IU\u2003ml<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A nonlinear mixed effects model was developed with NONMEM<jats:sup>\u00ae<\/jats:sup> for 48 adult patients who received CII of enoxaparin with infusion durations that ranged from 8 to 894\u2003h at rates between 100 and 1600\u2003IU\u2003h<jats:sup>\u22121<\/jats:sup>. Three hundred and sixty\u2010three anti\u2010Xa concentration measurements were available from patients who received CII. These were combined with 309 anti\u2010Xa concentrations from 35 patients who received subcutaneous enoxaparin. The effects of age, body size, height, sex, creatinine clearance (CrCL) and patient location [intensive care unit (ICU) or general medical unit] on pharmacokinetic (PK) parameters were evaluated. Monte Carlo simulations were used to (i) evaluate covariate effects on <jats:italic>C<\/jats:italic><jats:sub>ss<\/jats:sub> and (ii) compare the impact of different infusion rates on predicted <jats:italic>C<\/jats:italic><jats:sub>ss<\/jats:sub>. The best dose was selected based on the highest probability that the <jats:italic>C<\/jats:italic><jats:sub>ss<\/jats:sub> achieved would lie within the therapeutic range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A two\u2010compartment linear model with additive and proportional residual error for general medical unit patients and only a proportional error for patients in ICU provided the best description of the data. Both CrCL and weight were found to affect significantly clearance and volume of distribution of the central compartment, respectively. Simulations suggested that the best doses for patients in the ICU setting were 50\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> per 12\u2003h (4.2\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>) if CrCL &lt;\u200a30\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>; 60\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> per 12\u2003h (5.0\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>) if CrCL was 30\u201350\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>; and 70\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> per 12\u2003h (5.8\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>) if CrCL &gt;\u200a50\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>. The best doses for patients in the general medical unit were 60\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> per 12\u2003h (5.0\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>) if CrCL &lt;\u200a30\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>; 70\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> per 12\u2003h (5.8\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>) if CrCL was 30\u201350\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>; and 100\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> per 12\u2003h (8.3\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> h<jats:sup>\u22121<\/jats:sup>) if CrCL &gt;\u200a50\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>. These best doses were selected based on providing the lowest equal probability of either being above or below the therapeutic range and the highest probability that the <jats:italic>C<\/jats:italic><jats:sub>ss<\/jats:sub> achieved would lie within the therapeutic range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The dose of enoxaparin should be individualized to the patients\u2019 renal function and weight. There is some evidence to support slightly lower doses of CII enoxaparin in patients in the ICU setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02650.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T22:45:50Z","timestamp":1145659550000},"page":"165-176","source":"Crossref","is-referenced-by-count":14,"title":["Development of a dosage strategy in patients receiving enoxaparin by continuous intravenous infusion using modelling and simulation"],"prefix":"10.1111","volume":"62","author":[{"given":"Yan","family":"Feng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen B.","family":"Duffull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra 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