{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:46:36Z","timestamp":1766087196572,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T00:00:00Z","timestamp":1489622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015086","name":"AOP Orphan Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015086","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anagrelide is an established therapy for essential thrombocythemia. Common adverse effects have been linked to peak plasma concentrations of anagrelide and its 3OH metabolite. Our study was performed to investigate the pharmacokinetics (PK) of a novel anagrelide extended\u2010release (AER) formulation and its active metabolites. Thirty healthy volunteers were randomized to receive either 2 mg AER (under fasting and fed conditions) or 2 mg commercially available reference product (CARP) in an open\u2010label, 3\u2010way crossover trial with washout periods of 6 days. Plasma concentrations of anagrelide and its active metabolites were assessed by tandem mass spectrometry. The PK differed significantly between all treatment periods. Bioavailability of AER was 55% of the CARP under fasting conditions and 60% under fed conditions. C<jats:sub>max<\/jats:sub>, AUCt, and AUC\u221e were significantly higher and T<jats:sub>max<\/jats:sub> and T<jats:sub>1\/2<\/jats:sub> were significantly shorter after the CARP compared with AER. Food had a significant impact on the PK of AER, increasing the C<jats:sub>max<\/jats:sub> and AUC<jats:sub>t<\/jats:sub> while reducing the T<jats:sub>1\/2<\/jats:sub>, plateau, and mean residence time. Both formulations were well tolerated, with a trend toward more frequently occurring adverse events after the CARP. The PK of AER and the CARP differed significantly in all parameters. Food enhanced the bioavailability of AER.<\/jats:p>","DOI":"10.1002\/cpdd.340","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T16:54:29Z","timestamp":1489683269000},"page":"123-131","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacokinetics of a Novel Anagrelide Extended\u2010Release Formulation in Healthy Subjects: Food Intake and Comparison With a Reference Product"],"prefix":"10.1002","volume":"7","author":[{"given":"Petro E.","family":"Petrides","sequence":"first","affiliation":[{"name":"Hematology Oncology Center and Ludwig Maximilians University of Munich Medical School  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schoergenhofer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Widmann","sequence":"additional","affiliation":[{"name":"AOP Orphan Pharmaceuticals AG  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Jilma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph S.","family":"Klade","sequence":"additional","affiliation":[{"name":"AOP Orphan Pharmaceuticals AG  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-014-1631-x"},{"key":"e_1_2_10_3_1","unstructured":"PetridesPE GisslingerH BaerlocherGM Grie\u00dfhammerM LengfelderE.Essentielle (oder prim\u00e4re) Thrombozyth\u00e4mie (ET).www.onkopedia.com\/de\/onkopedia\/guidelines"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199447050-00007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198805193182002"},{"issue":"3","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1055\/s-0038-1661206","article-title":"Inhibition of platelet production induced by an antiplatelet drug, anagrelide, in normal volunteers","volume":"52","author":"Abe Andes W","year":"1984","journal-title":"Thromb Haemost."},{"issue":"8","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1182\/blood.V79.8.1931.1931","article-title":"Analysis of the mechanism of anagrelide\u2010induced thrombocytopenia in humans","volume":"79","author":"Mazur EM","year":"1992","journal-title":"Blood."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1602"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03970.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12959"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-443770"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043800"},{"issue":"8","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1517\/14656566.5.8.1781","article-title":"a decade of clinical experience with its use for the treatment of primary thrombocythaemia","volume":"5","author":"Anagrelide Petrides PE.","year":"2004","journal-title":"Expert Opin Pharmacother."},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2004.10.002"},{"issue":"4","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3324\/haematol.2012.083097","article-title":"Combination therapy of hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of Xagrid(R) efficacy and long\u2010term safety study","volume":"99","author":"Gugliotta L","year":"2014","journal-title":"Haematologica."},{"issue":"11","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.5414\/CP201711","article-title":"Pharmacokinetics and tolerability of anagrelide hydrochloride in young (18 \u2010 50 years) and elderly (>\/= 65 years) patients with essential thrombocythemia","volume":"50","author":"Besses C","year":"2012","journal-title":"Int J Clin Pharmacol Ther."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-012-0032-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2009.02.008"},{"key":"e_1_2_10_19_1","unstructured":"CPMP\/EWP\/280\/96 E. 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