{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:17:33Z","timestamp":1778149053759,"version":"3.51.4"},"reference-count":11,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":4784,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p>The pharmacokinetics and safety of duloxetine were evaluated in a single\u2010blind, placebo\u2010controlled, escalating multiple\u2010dose study in 12 healthy male subjects. In the treatment group (n = 8), duloxetine was administered orally at a starting dose of 20 mg twice daily (bid) and escalated at weekly intervals to 30 mg bid, then to 40 mg bid. The observed plasma concentration\u2010time data at all three dose levels were adequately described by a one\u2010compartment model with a first\u2010order absorption rate constant. The mean oral clearance, apparent volume of distribution, and half\u2010life values were 114 L\/h (range: 44 to 218 L\/h), 1943 L (range: 803 to 3531 L), and 12.5 h (range: 9.2 to 19.1 h), respectively. Somnolence, nausea, and dry mouth were observed following the initial dose, but they resolved with continuing drug administration. Duloxetine was not associated with clinically significant changes in blood pressure (BP) or heart rate (HR) measured in the standing position. However, in recumbent position, small increases in systolic (\u2264 9 mmHg) and diastolic (\u2264 5 mmHg) BP and small decreases in HR (\u2264 6 beats\/min) were observed. Abrupt discontinuation of duloxetine was associated with a small increase in mean HR (\u2264 12beats\/min). In 3 subjects, abrupt discontinuation was also associated with transient sleep disturbance. No clinically important changes in electrocardiograms, cardiac intervals, clinical laboratory tests, and neurological functions were observed. These results indicate that duloxetine exhibits linear pharmacokinetics with respect to dose and duration of treatment and that a multiple oral dose regimen starting at 20 mg bid and gradually escalating up to 40 mg bid was generally well tolerated.<\/jats:p>","DOI":"10.1177\/00912700022008810","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"161-167","source":"Crossref","is-referenced-by-count":113,"title":["Pharmacokinetics and Safety of Duloxetine, a Dual\u2010Serotonin and Norepinephrine Reuptake Inhibitor"],"prefix":"10.1002","volume":"40","author":[{"given":"Amarnath","family":"Sharma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benito J.","family":"Cerimele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.1993.4"},{"key":"e_1_2_1_3_2","first-page":"278","article-title":"Blockade of the serotonin and norepinephrine uptake processes by duloxetine: in vitro and in vivo studies in the rat brain","volume":"277","author":"Kasamo K","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_4_2","first-page":"1067","article-title":"Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats","volume":"272","author":"Katoh A","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_5_2","first-page":"1014","article-title":"Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose\u2010anesthetized female cat","volume":"274","author":"Thor KB","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-468X(79)90025-4"},{"key":"e_1_2_1_7_2","volume-title":"ADAPT II Users' Guide.","author":"D'Argenio DZ","year":"1992"},{"key":"e_1_2_1_8_2","volume-title":"SAS\/STAT User's Guide, version 6","author":"SAS Institute","year":"1989"},{"key":"e_1_2_1_9_2","volume-title":"LY2486876 (duloxetine): 14C\u2010LY248686 study of absorption, distribution, metabolism, and excretion in healthy human subjects","author":"DeLong AF","year":"1996"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/hup.470100907"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(98)00126-7"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1996.tb02965.x"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F00912700022008810","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/00912700022008810","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T08:28:01Z","timestamp":1698568081000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/00912700022008810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2]]},"references-count":11,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,2]]}},"alternative-id":["10.1177\/00912700022008810"],"URL":"https:\/\/doi.org\/10.1177\/00912700022008810","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,2]]}}}