{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T03:59:08Z","timestamp":1767153548774,"version":"build-2238731810"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,11,1]]},"abstract":"1.Renal specific targeting of the non-steroidal anti-inflammatory drug naproxen was obtained by coupling to the low-molecular-mass protein lysozyme. A previous study showed that conjugation to lysozyme resulted in a 70-fold increase of naproxen accumulation in the kidney with a subsequent renal release of the active metabolite naproxen\u2013lysine.<\/jats:p>\n 2.In the present study we questioned whether naproxen\u2013lysozyme is active in the rat kidney, inhibiting the urinary excretion of prostaglandin E2 and renal sodium and water excretion in salt-restricted baseline conditions as well as during frusemide treatment.<\/jats:p>\n 3.A high dose of free naproxen (10 ;mg\u00b7day-1\u00b7kg-1) did not affect prostaglandin E2 excretion in baseline conditions (naproxen, 11\u00b11 ;ng\/8 ;h; vehicle, 13\u00b14 ;ng\/8 ;h), whereas sodium and water excretion were, respectively, 3.0 and 1.6 times lower in the naproxen group (P&lt; 0.05). Naproxen completely prevented the frusemide-induced increase (3-fold) in prostaglandin E2 excretion (naproxen 6.6\u00b11.1 ;ng\/8 ;h, vehicle 40\u00b112 ;ng\/8 ;h, P&lt; 0.005). Frusemide-stimulated natriuresis and diuresis were, respectively, 1.6 (P&lt; 0.05) and 1.8 times (P&lt; 0.005) lower in the naproxen group.<\/jats:p>\n 4.A dose of 2 ;mg\u00b7day-1\u00b7kg-1 lysozyme-conjugated naproxen did not affect prostaglandin E2 excretion in baseline conditions (conjugate, 18\u00b12 ;ng\/8 ;h; vehicle, 24\u00b15 ;ng\/8 ;h). The conjugate also had no effect on sodium and water excretion. However, the naproxen conjugate completely prevented the frusemide-induced increase (2-fold) in prostaglandin E2 excretion (conjugate, 16\u00b13 ;ng\/8 ;h; vehicle, 48\u00b113 ;ng\/8 ;h, P&lt; 0.05). Surprisingly, frusemide-induced natriuresis and diuresis were not affected by the conjugate.<\/jats:p>\n 5.In conclusion, a renal specific delivery of the non-steroidal anti-inflammatory drug naproxen using lysozyme results in an inhibitory effect on renal prostaglandin E2 synthesis but does not affect the excretion of sodium and water, in contrast to free naproxen.<\/jats:p>","DOI":"10.1042\/cs0950603","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T07:40:53Z","timestamp":1438933253000},"page":"603-609","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Renal targeting of a non-steroidal anti-inflammatory drug: effects on renal prostaglandin synthesis in the rat"],"prefix":"10.1042","volume":"95","author":[{"given":"Marijke","family":"HAAS","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Groningen Institute for Drug Studies, University Hospital, Hanzeplein 1, NL-9713 GZ Groningen, The Netherlands"},{"name":"Department of Clinical Pharmacology, Groningen Institute for Drug Studies, University of Groningen, Ant. Deusinglaan 1, NL-9713 AV Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frits","family":"MOOLENAAR","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Drug Delivery, Groningen Institute for Drug Studies, University of Groningen, Ant. Deusinglaan 1, NL-9713 AV Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk K. F.","family":"MEIJER","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Drug Delivery, Groningen Institute for Drug Studies, University of Groningen, Ant. Deusinglaan 1, NL-9713 AV Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul E. DE","family":"JONG","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Groningen Institute for Drug Studies, University Hospital, Hanzeplein 1, NL-9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick DE","family":"ZEEUW","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Groningen Institute for Drug Studies, University Hospital, Hanzeplein 1, NL-9713 GZ Groningen, The Netherlands"},{"name":"Department of Clinical Pharmacology, Groningen Institute for Drug Studies, University of Groningen, Ant. Deusinglaan 1, NL-9713 AV Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/95\/5\/603\/467340\/cs0950603.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/95\/5\/603\/467340\/cs0950603.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T20:17:28Z","timestamp":1684095448000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/95\/5\/603\/77098\/Renal-targeting-of-a-non-steroidal-anti"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,11,1]]},"references-count":0,"aliases":["10.1042\/cs19980188"],"journal-issue":{"issue":"5","published-print":{"date-parts":[[1998,11,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs0950603","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,11,1]]}}}