{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:08:22Z","timestamp":1759961302834,"version":"3.28.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"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":[[2004,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Desmopressin is a synthetic vasopressin analogue mainly used in treatment of diabetes insipidus and nocturia. Studies in rats have revealed a sex difference in the response to a vasopressin infusion, which was diminished after treatment with an NSAID. This study was performed in man to investigate the influence of sex and concomitant treatment of piroxicam on the pharmacokinetics and dynamics of desmopressin, and to validate a previously described indirect response model. Eight healthy males and eight healthy females participated in the trial, which was conducted in a pharmacokinetic (PK) part followed by a pharmacodynamic (PD) part. Desmopressin was administered intravenously as a single dose (PK = dose 2 \u03bcg, PD = dose 0.2 \u03bcg). Piroxicam was administered to achieve steady state. The pharmacokinetic parameters of desmopressin were estimated and calculated by means of two-compartmental analysis. In the dynamic part a study design based on an oral hydration model was used. Parameters for urine flow and urine osmolality were estimated. Individual estimates of the pharmacokinetic parameters served as input to the indirect response model that subsequently was fitted to urine osmolality data. The pharmacokinetics of desmopressin after a fixed bolus injection was neither influenced by piroxicam nor sex of the subject. The pharmacodynamics of desmopressin showed a sex difference where females exhibited a more pronounced antidiuretic effect than males, which was statistically significant when the effects were submaximal (&amp;gt;4.5 h after dose). The sex differences were diminished after pre-treatment with piroxicam, indicating a prostaglandin PGE2-mediated mechanism. The indirect response model was confirmed, although the modelling could not distinguish a sex difference, indicating a limitation of this model compared with traditional descriptive statistics.<\/jats:p>","DOI":"10.1211\/0022357044535","type":"journal-article","created":{"date-parts":[[2004,10,28]],"date-time":"2004-10-28T09:39:48Z","timestamp":1098956388000},"page":"1389-1398","source":"Crossref","is-referenced-by-count":11,"title":["A pharmacokinetic and pharmacodynamic study of desmopressin: evaluating sex differences and the effect of pre-treatment with piroxicam, and further validation of an indirect response model"],"prefix":"10.1093","volume":"56","author":[{"given":"Johanna Mercke","family":"Odeberg","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Pharmacology, University Hospital Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torbj\u00f6rn","family":"Callr\u00e9us","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pharmacology, University Hospital Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pharmacology, University Hospital Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E Bodil","family":"Roth","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Malm\u00f6 University Hospital , Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"H\u00f6glund","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pharmacology, University Hospital Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,11,1]]},"reference":[{"key":"2024103109410035900_cit1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1054\/plef.2002.0428","article-title":"Low-dose desmopressin infusion: renal action in healthy women in moderate salt retention and depletion, and interactions with prostanoids","volume":"67","author":"Agnoli","year":"2002","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"2024103109410035900_cit2","first-page":"529","article-title":"Gender differences in pharmacokinetics and pharmacodynamics","volume":"37","author":"Beierle","year":"1999","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"2024103109410035900_cit3","doi-asserted-by":"crossref","first-page":"F12","DOI":"10.1152\/ajprenal.2000.279.1.F12","article-title":"Prostaglandin E receptors and the kidney","volume":"279","author":"Breyer","year":"2000","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"2024103109410035900_cit4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1600-0773.1998.tb01479.x","article-title":"Pharmacokinetics and antidiuretic effect of intravenous administration of desmopressin in orally overhydrated male volunteers","volume":"83","author":"Callr\u00e9us","year":"1998","journal-title":"Pharmacol. Toxicol."},{"key":"2024103109410035900_cit5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1023\/A:1023238514015","article-title":"Indirect-response modeling of desmopressin at different levels of hydration","volume":"27","author":"Callr\u00e9us","year":"1999","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"2024103109410035900_cit6","first-page":"159","article-title":"Stimulation of prostaglandin E2 biosynthesis by estradiol in rat kidneys","volume":"33","author":"Chang","year":"1988","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"2024103109410035900_cit7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/BF01061691","article-title":"Comparison of four basic models of indirect pharmacodynamic responses","volume":"21","author":"Dayneka","year":"1993","journal-title":"J. Pharmacokinet. 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