{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T16:33:08Z","timestamp":1770222788760,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>A pharmacokinetic\/pharmacodynamic modelling approach was used to determine a dosage regimen which maximizes diuretic efficiency of torasemide in dogs. Kinetic profiles of plasma concentration, torasemide excretion rate in urine (<jats:styled-content style=\"fixed-case\">TERU<\/jats:styled-content>) and diuresis were investigated in 10\u00a0dogs after single oral administrations at 3 dose levels, 0.2, 0.8 and 1.6\u00a0mg\/kg, and an intravenous injection of 0.2\u00a0mg\/kg. Endogenous regulation was evidenced by a proteresis loop between<jats:styled-content style=\"fixed-case\">TERU<\/jats:styled-content>and diuresis. To describe the diuresis\u2013time profile,<jats:styled-content style=\"fixed-case\">TERU<\/jats:styled-content>served as input into a turnover model with inhibition of loss of response, extended by a moderator acting on both loss and production of response. Estimated maximum inhibition of loss of response,<jats:italic>I<\/jats:italic><jats:sub>max<\/jats:sub>, was 0.984 showing that torasemide is an efficacious diuretic able to suppress almost total water reabsorption. A<jats:styled-content style=\"fixed-case\">TERU<\/jats:styled-content><jats:sub>50,<\/jats:sub>value producing half of<jats:italic>I<\/jats:italic><jats:sub>max<\/jats:sub>, of 1.45\u00a0\u03bcg\/kg\/h was estimated from the model. Pharmacokinetic and pharmacodynamic parameters were used to simulate the torasemide dose\u2013effect relationship after oral administration. Model predictions were in good agreement with diuresis measured in a validation study conducted in 10 dogs, which were administered oral doses of 0.15, 0.4, 0.75, 1.5 and 4.5\u00a0mg\/kg for 5\u00a0days. Finally, oral dose associated with the highest daily diuretic efficiency was predicted to be 0.1\u00a0mg\/kg.<\/jats:p>","DOI":"10.1111\/jvp.12316","type":"journal-article","created":{"date-parts":[[2016,5,27]],"date-time":"2016-05-27T05:01:28Z","timestamp":1464325288000},"page":"547-559","source":"Crossref","is-referenced-by-count":10,"title":["A pharmacokinetic\/pharmacodynamic model capturing the time course of torasemide\u2010induced diuresis in the dog"],"prefix":"10.1111","volume":"39","author":[{"given":"A.","family":"Paulin","sequence":"first","affiliation":[{"name":"Global Drug Development Division V\u00e9toquinol S.A. Lure France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Global Drug Development Division V\u00e9toquinol S.A. 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