{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T04:09:37Z","timestamp":1754194177171},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,6,12]],"date-time":"2014-06-12T00:00:00Z","timestamp":1402531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,6,12]],"date-time":"2014-06-12T00:00:00Z","timestamp":1402531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["In Silico Pharmacol."],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Gadofosveset is a Gd-based contrast agent used for magnetic resonance imaging (MRI). Gadolinium kinetic distribution models are implemented in T1-weighted dynamic contrast-enhanced perfusion MRI for characterization of lesion sites in the body. Physiology changes in a disease state potentially can influence the pharmacokinetics of drugs and to this respect modify the distribution properties of contrast agents. This work focuses on the <jats:italic>in silico<\/jats:italic> modelling of pharmacokinetic properties of gadofosveset in different population groups through the application of physiologically-based pharmacokinetic models (PBPK) embedded in Simcyp\u00ae population pharmacokinetics platform.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Physicochemical and pharmacokinetic properties of gadofosveset were introduced into Simcyp\u00ae simulator platform and a min-PBPK model was applied. <jats:italic>In silico<\/jats:italic> clinical trials were generated simulating the administration of the recommended dose for the contrast agent (i.v., 30\u00a0mg\/kg) in population cohorts of healthy volunteers, obese, renal and liver impairment, and in a generated virtual oncology population. Results were evaluated regarding basic pharmacokinetic parameters of Cmax, AUC and systemic CL and differences were assessed through ANOVA and estimation of ratio of geometric mean between healthy volunteers and the other population groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Simcyp\u00ae predicted a mean Cmax\u2009=\u2009551.60\u00a0mg\/l, a mean AUC\u2009=\u20094079.12\u00a0mg\/L*h and a mean systemic CL\u2009=\u20090.56\u00a0L\/h for the virtual population of healthy volunteers. Obese population showed a modulation in Cmax and CL, attributed to increased administered dose. In renal and liver impairment cohorts a significant modulation in Cmax, AUC and CL of gadofosveset is predicted. Oncology population exhibited statistical significant differences regarding AUC when compared with healthy volunteers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This work employed Simcyp\u00ae population pharmacokinetics platform in order to compute gadofosveset\u2019s pharmacokinetic profiles through PBPK models and <jats:italic>in silico<\/jats:italic> clinical trials and evaluate possible differences between population groups. The approach showed promising results that could provide new insights regarding administration of contrast agents in special population cohorts. <jats:italic>In silico<\/jats:italic> pharmacokinetics could further be used for evaluating of possible toxicity, interpretation of MRI PK image maps and development of novel contrast agents.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40203-014-0002-x","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T08:52:57Z","timestamp":1402476777000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In silico evaluation of gadofosveset pharmacokinetics in different population groups using the Simcyp\u00ae simulator platform"],"prefix":"10.1186","volume":"2","author":[{"given":"Marios","family":"Spanakis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kostas","family":"Marias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,6,12]]},"reference":[{"issue":"2","key":"2_CR1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.ejrad.2008.01.026","volume":"66","author":"JL Abraham","year":"2008","unstructured":"Abraham JL, Thakral C: Tissue distribution and kinetics of gadolinium and nephrogenic systemic fibrosis. 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