{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T07:21:36Z","timestamp":1765524096754,"version":"3.48.0"},"reference-count":42,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    In order to identify a suitable rodent model for preclinical study of calcium antagonists, the pharmacokinetics and metabolism of one of the prototypes diltiazem (DTZ) in normotensive Sprague Dawley (SDR) was compared with Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) following 5\u00a0mg\/kg twice daily for five doses given by subcutaneous injection.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Pharmacokinetic data were analyzed by standard procedures assuming a one-compartment model with first-order input using Rstrips\n                    <jats:sup>\u00ae<\/jats:sup>\n                    , and differences between the groups were considered significant when p&lt;0.05.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Plasma concentrations of DTZ were higher in the SHR than the normotensive SDR and WKY rats, although the differences did not reach statistical significance (p&gt;0.05). Plasma concentrations of the active metabolites N-desmethyl DTZ (MA), deacetyl DTZ (M1) and deacetyl N-desmethyl DTZ (M2) were significantly higher in the SHR and WKY rats than the SDR, which was attributed to higher DTZ concentrations and also genetic factors.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Although the differences were mainly quantitative and very small, the study has shown for the first time that the metabolism profiles of DTZ in SHR and WKY rats were closer to humans than SDR, and they may be more preferable rat models to study pharmacokinetic and metabolism studies of DTZ or similar agents.\n                  <\/jats:p>","DOI":"10.1515\/dmdi.2011.012","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T08:24:05Z","timestamp":1316507045000},"page":"119-125","source":"Crossref","is-referenced-by-count":1,"title":["Comparing pharmacokinetics and 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