{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:32:09Z","timestamp":1791019929977,"version":"4.1.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The aim was to investigate the pharmacokinetics of morphine and its metabolite, morphine-3-glucuronide (M3G), in a rat model of streptozotocin (STZ)-induced diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Morphine (15 mg\/kg) was administered intravenously, and the concentrations of morphine and M3G in the plasma, urine and bile were measured by HPLC. Changes in the expression of multidrug resistance-associated proteins (MRP2 and MRP3) and UDP-glucuronosyltransferase 2B1 (UGT2B1) mRNA in the liver were also estimated by reverse-transcriptase PCR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Plasma morphine concentrations were lower in the STZ-diabetic rats than controls although the elimination half-life of morphine was similar in the two groups (47.9 \u00b1 10.7 min and 47.2 \u00b1 8.6 min, respectively). The concentration of M3G in plasma was higher in STZ-diabetic than control rats, and the biliary excretion of M3G was lower in the STZ-diabetic rats (7.4 \u00b1 2.3% vs 13.3 \u00b1 2.0%). The urinary excretion of M3G was similar in the two groups (10.1 \u00b1 6.8% vs 10.9 \u00b1 4.9%). The expression of MRP3 and UGT2B1 mRNA was increased in STZ-diabetic rats, whereas expression of MRP2 mRNA was decreased.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In STZ-diabetic rats, the distribution volume of morphine increased, the glucuronidation rate and M3G transportation into the blood were enhanced, and the excretion of M3G was decreased, leading to an increase in the plasma M3G concentration.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1211\/jpp.62.03.0004","type":"journal-article","created":{"date-parts":[[2010,10,14]],"date-time":"2010-10-14T12:03:16Z","timestamp":1287057796000},"page":"310-314","source":"Crossref","is-referenced-by-count":34,"title":["The pharmacokinetics of morphine and its glucuronide conjugate in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2B1 in the liver"],"prefix":"10.1093","volume":"62","author":[{"given":"Yoshitaka","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]},{"name":"Cooperative Research Center of Life Science, Kobe Gakuin University , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]},{"name":"Cooperative Research Center of Life Science, Kobe Gakuin University , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Shibatani","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Nomura","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ishii","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Onishi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Inotsume","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy , Otaru,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences , Kobe,","place":["Japan"]},{"name":"Cooperative Research Center of Life Science, Kobe Gakuin University , Kobe,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,3,1]]},"reference":[{"key":"2024103013101283700_cit1","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.1073\/pnas.0502530102","article-title":"Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide 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