{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T09:15:48Z","timestamp":1760865348967},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":1861,"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":[[2008,2]]},"abstract":"<jats:p>The authors evaluate the human safety, tolerability, pharmacokinetics, and pharmacodynamics of TZP\u2010101, an agonist of the hGHS\u2010R1a (ghrelin) receptor. Healthy subjects were randomized to either single\u2010dose TZP\u2010101 (20\u2013600 \u03bcg\/kg) or placebo by 30\u2010minute intravenous infusion. Subjects underwent continuous cardiac monitoring, 12\u2010lead electrocardiograms, and assessment for orthostatic hypotension, injection site tolerability, vital signs, and adverse events during the 24\u2010hour postdose period. Blood and urine samples were collected for pharmacokinetic\/pharmacodynamic assessment for 24 hours. Forty\u2010eight subjects randomly received 1 of 6 TZP\u2010101 doses or placebo. TZP\u2010101 was well tolerated, with single episodes each of headache, lower abdominal pain, diarrhea, and dizziness. At the highest dose, 2 subjects experienced bradycardia. All events were self\u2010limited. Mean arterial blood pressure and heart rate decreased from baseline approximately 45 to 60 minutes after infusion start at higher doses. No other significant changes were observed. Pharmacokinetic analysis revealed less than dose\u2010proportional behavior of drug with low clearance (\u22457 mL\/h\/kg), small volume of distribution (\u2245114 mL\/kg), and half\u2010life values of \u224513 hours, which were independent of dose. Pharmacodynamic analyses suggested TZP\u2010101, at doses as low as 40 \u03bcg\/kg, expressed activity at the receptor. TZP\u2010101 displayed a promising pharmacokinetic, pharmacodynamic, and safety profile for use in gastrointestinal motility disorders.<\/jats:p>","DOI":"10.1177\/0091270007310380","type":"journal-article","created":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T02:25:00Z","timestamp":1200536700000},"page":"193-202","source":"Crossref","is-referenced-by-count":60,"title":["Ghrelin Agonist (TZP\u2010101): Safety, Pharmacokinetics and Pharmacodynamic Evaluation in Healthy Volunteers: A Phase I, First\u2010in\u2010Human Study"],"prefix":"10.1002","volume":"48","author":[{"given":"Kenneth C.","family":"Lasseter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Shaughnessy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Cummings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Pezzullo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Wargin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene","family":"Gagnon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordana","family":"Kosutic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2006.05.022"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2638"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00327-0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.040600"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.04.001"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.065896"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(01)00557-5"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00339.2001"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(03)00113-X"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.02.010"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.069088"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.12.008"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.060426"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0223-5234(00)00146-X"},{"issue":"2","key":"e_1_2_6_16_2","article-title":"Pharmacological separation of the gastrointestinal and endocrine effects of ghrelin using a novel GHS\u2010R1a agonist","volume":"17","author":"Fraser GL","year":"2005","journal-title":"Neurogastroenterol Motil."},{"key":"e_1_2_6_17_2","unstructured":"VenkovaK FraserG HoveydaH et al.Ghrelin agonist activity in a rat model of postoperative ileus and opioid\u2010delayed gastrointestinal motility. 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