{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T19:23:25Z","timestamp":1774293805354,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010721","name":"Ironwood Pharmaceuticals, Incorporated","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010721","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Renal impairment is a common complication in patients with short bowel syndrome with intestinal failure (SBS\u2010IF). Glucagon\u2010like peptide\u20102 analogs, such as apraglutide, have been developed as a treatment option for SBS\u2010IF. This study assessed the potential for apraglutide overexposure in individuals with severely impaired renal function versus healthy volunteers with normal renal function. In this phase 1, open\u2010label, multicenter, nonrandomized, parallel\u2010group study, a single dose of apraglutide 5 mg was administered subcutaneously to individuals with severely impaired renal function (&lt;30 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>) and healthy volunteers with normal renal function (\u226590\u00a0mL\/min\/1.73 m<jats:sup>2<\/jats:sup>). Primary pharmacokinetic endpoints were maximum observed concentration (C<jats:sub>max<\/jats:sub>) and exposure to apraglutide (area under the curve [AUC] from time 0 to infinity [AUC<jats:sub>inf<\/jats:sub>], and AUC from time 0 to the last quantifiable concentration [AUC<jats:sub>last<\/jats:sub>]). Each group comprised 8 individuals. Results show that patients with severe renal impairment do not have increased apraglutide exposure. Apraglutide achieved a lower C<jats:sub>max<\/jats:sub> and AUC<jats:sub>inf<\/jats:sub> in individuals with severe renal impairment versus those with normal renal function (C<jats:sub>max<\/jats:sub> = 36.9 vs 59.5 ng\/L; AUC<jats:sub>inf<\/jats:sub> = 3100 vs 4470 h \u00b7 ng\/mL, respectively). The respective geometric mean ratios were 0.620 and 0.693 for C<jats:sub>max<\/jats:sub> and AUC<jats:sub>inf<\/jats:sub>, and the upper bound of their 90% confidence intervals were &lt;2, indicating patients with severe renal impairment were not overexposed to apraglutide versus those with normal renal function. Adverse events were mild or moderate in severity. Apraglutide does not require dose reduction for any degree of renal impairment and could be used in a broader patient population of renally impaired patients without dose adjustment.<\/jats:p>","DOI":"10.1002\/jcph.2423","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T09:34:19Z","timestamp":1710149659000},"page":"744-754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long\u2010Acting, Synthetic glucagon\u2010like peptide\u20102 Analog With a Unique Pharmacologic Profile, in Individuals With Impaired Renal Function"],"prefix":"10.1002","volume":"64","author":[{"given":"G\u00e9rard","family":"Greig","sequence":"first","affiliation":[{"name":"Ironwood Pharmaceuticals Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nader N","family":"Youssef","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Bolognani","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2019.11.013"},{"key":"e_1_2_11_3_1","unstructured":"National Organization for Rare Disorders.Short bowel syndrome.https:\/\/rarediseases.org\/rare\u2010diseases\/short\u2010bowel\u2010syndrome\/. Accessed October 4 2023"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2005.10.002"},{"issue":"10","key":"e_1_2_11_5_1","first-page":"1297","article-title":"Short bowel syndrome: a nutritional and medical approach","volume":"166","author":"Jeejeebhoy KN","year":"2002","journal-title":"CMAJ"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.762240"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.1053"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.262238"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2020.618758"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2017.07.011"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607100024004234"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607193017005438"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2005.09.010"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.3.428"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000046"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2017.1304912"},{"key":"e_1_2_11_17_1","unstructured":"Revestive\u00ae (teduglutide).Summary of product characteristics. Takeda; 2022.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/revestive\u2010epar\u2010product\u2010information_en.pdf. Accessed October 4 2023."},{"key":"e_1_2_11_18_1","unstructured":"Gattex (teduglutide).US prescribing information. Takeda; 2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/203441s013lbl.pdf. Accessed October 4 2023."},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.09.007"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01909"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.123.001582"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008320605"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2223"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.2362"},{"key":"e_1_2_11_25_1","unstructured":"VectivBio.Data on file. VectivBio Investigator's Brochure Apraglutide Version8.0;2023."},{"key":"e_1_2_11_26_1","unstructured":"U.S. Food and Drug Administration.Code of federal regulations \u2010 title 21 \u2010 food and drugs.https:\/\/www.fda.gov\/medical\u2010devices\/medical\u2010device\u2010databases\/code\u2010federal\u2010regulations\u2010title\u201021\u2010food\u2010and\u2010drugs. Accessed October 4 2023."},{"key":"e_1_2_11_27_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline. Bioanalytical method validation and study sample analysis M10.https:\/\/database.ich.org\/sites\/default\/files\/M10_Guideline_Step4_2022_0524.pdf. 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