{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T10:15:15Z","timestamp":1793528115457,"version":"4.5.0"},"reference-count":22,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dmpt-2016-0008_s_999_w2aab2b8b7b1b7b1aab1c15b1Aa\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Severe forms of non-alcoholic fatty liver disease (NAFLD) adversely affect the liver physiology and hence the pharmacokinetics of drugs. Here, we investigated the effect of NAFLD on the pharmacokinetics of rosiglitazone, an insulin sensitizer used in the treatment of type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2016-0008_s_998_w2aab2b8b7b1b7b1aab1c15b2Aa\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Male C57BL\/6 mice were divided into two groups. The first group (n=14) was fed with normal chow feed and the second group (n=14) was fed with 60% high-fat diet (HFD) and 40% high fructose liquid (HFL) for 60 days to induce NAFLD. The development of NAFLD was confirmed by histopathology, liver triglyceride levels and biochemical estimations, and used for pharmacokinetic investigations. Rosiglitazone was administered orally at 30 mg\/kg dose. At predetermined time points, blood was collected and rosiglitazone concentrations were determined using LC\/MS\/MS. Plasma concentrations were subjected to non-compartmental analysis using Phoenix WinNonlin (6.3), and the area under the plasma concentration-time curve (AUC) was calculated by the linear-up log-down method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2016-0008_s_997_w2aab2b8b7b1b7b1aab1c15b3Aa\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>HFD and HFL diet successfully induced NAFLD in mice. Rosiglitazone pharmacokinetics in NAFLD animals were altered significantly as compared to healthy mice. Rosiglitazone exposure increased significantly in NAFLD mice (2.5-fold higher AUC than healthy mice). The rosiglitazone oral clearance was significantly lower and the mean plasma half-life was significantly longer in NAFLD mice as compared to healthy mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dmpt-2016-0008_s_996_w2aab2b8b7b1b7b1aab1c15b4Aa\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The NAFLD mouse model showed profound effects on rosiglitazone pharmacokinetics. The magnitude of change in rosiglitazone pharmacokinetics is similar to that observed in humans with moderate to severe liver disease. The present animal model can be utilized to study the NAFLD-induced changes in the pharmacokinetics of different drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dmpt-2016-0008","type":"journal-article","created":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T10:31:37Z","timestamp":1471257097000},"page":"165-171","source":"Crossref","is-referenced-by-count":12,"title":["Altered pharmacokinetics of rosiglitazone in a mouse model of non-alcoholic fatty liver disease"],"prefix":"10.1515","volume":"31","author":[{"given":"Nagaraj M.","family":"Kulkarni","sequence":"first","affiliation":[{"name":"Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Shozhanganallur, Chennai, India"},{"name":"Centre for Nanotechnology and Advanced Biomaterials (CeNTAB), School of Chemical and Biotechnology, SASTRA University, Thanjavur, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Malampati","sequence":"additional","affiliation":[{"name":"Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Shozhanganallur, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahamad Yunnus A.","family":"Mahat","sequence":"additional","affiliation":[{"name":"Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Shozhanganallur, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Shozhanganallur, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Raghul","sequence":"additional","affiliation":[{"name":"Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Shozhanganallur, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansar Ali","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd., Shozhanganallur, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma Maheswari","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Centre for Nanotechnology and Advanced Biomaterials (CeNTAB), School of Chemical and Biotechnology, SASTRA University, Thanjavur, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shridhar","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Centre for Nanotechnology and Advanced Biomaterials (CeNTAB), School of Chemical and Biotechnology, SASTRA University, Thanjavur, India"},{"name":"Foundation for Neglected Disease Research, 1st and 2nd Floors, Sri Krishnadevaraya Research Centre, Sir M. 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