{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:46:15Z","timestamp":1768981575561,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T00:00:00Z","timestamp":1565740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The angiotensin\u2010converting enzyme inhibitor enalapril is commonly used to treat chronic heart failure in children. Because some children are unable to swallow capsules or tablets, a new, age\u2010appropriate, orodispersible minitablet (ODMT) containing 1\u00a0mg of enalapril was developed within the EU\u2010funded LENA (Labeling of Enalapril from Neonates up to Adolescents) consortium. In order to support the clinical evaluation of this new formulation in children, a relative bioavailability study was performed in healthy adults, comparing the bioavailability of enalapril in the ODMT with that of a reference product (RP) Renitec, a registered standard enalapril tablet formulation. In this open\u2010label, randomized 3\u2010way crossover study, 24 healthy subjects received a 10\u2010mg enalapril dose administered as (1) 2\u00a0\u00d7\u00a05\u2010mg tablets of the RP swallowed with water, (2) 10\u00a0\u00d7\u00a01\u2010mg ODMT swallowed with water, and (3) 10\u00a0\u00d7\u00a01\u00a0mg ODMT dispersed on the tongue. When the relative bioavailability of the ODMT formulation swallowed with water was compared with that of the RP, the estimated 90%CIs for the ratio of area under the concentration\u2010time curve (AUC<jats:sub>0\u2010\u221e<\/jats:sub>) and or peak concentration (C<jats:sub>max<\/jats:sub>) of enalapril were 92.34% to 106.49% and 91.28% to 115.72%, respectively, which are within the accepted bioequivalence limits of 80% to 125%. Following dispersion of the ODMT in the mouth, a slightly higher C<jats:sub>max<\/jats:sub> for enalapril was observed as compared with the RP with an upper 90%CI of 127.57%, slightly exceeding the bioequivalence limit. Taken together, it was demonstrated that the method of administration of the ODMT, swallowed or dispersed, did not significantly affect the bioavailability of enalapril.<\/jats:p>","DOI":"10.1002\/cpdd.728","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T10:09:52Z","timestamp":1565777392000},"page":"203-213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults"],"prefix":"10.1002","volume":"9","author":[{"given":"Anne","family":"Van Hecken","sequence":"first","affiliation":[{"name":"Center for Clinical Pharmacology University Hospitals of Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn B.","family":"Burckhardt","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy and Pharmacotherapy Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feras","family":"Khalil","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy and Pharmacotherapy Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"de Hoon","sequence":"additional","affiliation":[{"name":"Center for Clinical Pharmacology University Hospitals of Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Klingmann","sequence":"additional","affiliation":[{"name":"Pharmaplex bvba  Wezembeek\u2010Oppem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"Herbots","sequence":"additional","affiliation":[{"name":"Center for Clinical Pharmacology University Hospitals of Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Laeer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy and Pharmacotherapy Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian B.","family":"Lagler","sequence":"additional","affiliation":[{"name":"Paracelsus Medical University  Salzburg Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Breitkreutz","sequence":"additional","affiliation":[{"name":"Ethicare GmbH  Haltern am See Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2018.1420054"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127002401102786"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1058-9813(00)00061-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.64.2.219"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)90749-O"},{"issue":"1","key":"e_1_2_8_7_1","first-page":"17","article-title":"Pediatric oral formulations: a continual challenge","volume":"11","author":"Hurtado J","year":"2007","journal-title":"Int J Pharm Compd"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-016-0527-x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199325040-00003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612820666141024151119"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198500301-00004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.04.019"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2011.02.005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1998.tb06876.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-003-0036-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.03.012"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425247.2011.553217"},{"key":"e_1_2_8_18_1","unstructured":"European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). Guideline on bioanalytical method validation.https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-bioanalytical-method-validation_en.pdf. Accessed August 1 2019."},{"key":"e_1_2_8_19_1","unstructured":"US Center for Drug Evaluation and Research Food and Drug Administration (FDA). Bioanalytical method validation guidance for industry.https:\/\/www.fda.gov\/media\/70858\/download. Accessed August 1 2019."},{"key":"e_1_2_8_20_1","unstructured":"European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). Guideline on the investigation of bioequivalence.https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-investigation-bioequivalence-rev1_en.pdf. Accessed August 1 2019."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1984.tb02601.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2004.09.031"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.10.012"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.129"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/796249"},{"key":"e_1_2_8_26_1","first-page":"117","article-title":"Model\u2010dependent pharmacokinetic analysis of enalapril administered to healthy adult volunteers using orodispersible minitablets for use in paediatrics","volume":"18","author":"Faisal M","year":"2018","journal-title":"Paediatrics."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2014.03.057"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.07.010"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.07.014"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-018-1080-4"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.728","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.728","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T10:24:35Z","timestamp":1694168675000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,14]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1002\/cpdd.728"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.728","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,14]]},"assertion":[{"value":"2019-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}