{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T08:47:26Z","timestamp":1694249246843},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>In this paper, a special case for bioequivalence evaluation of oral formulations is discussed. Drug formulations with different forms of active moieties (e.g., free base and salt) may yield different dissolution characteristics and, thus, differ in absorption at elevated gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>. However, routine bioequivalence trials using subjects with normal gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> (i.e., ~\u00a01) may fail to identify these differences because dissolution\/absorption profiles of the two formulations at normal gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> are similar. In the case of palbociclib, it is confirmedthat the free base and salt formulations showed different absorption in patients with different gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>. Significant reduction in drug absorption was observed only in patients with elevated gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> using free base formulation. The discovery that the free base had significantly reduced absorption hinged on the inclusion of enough patients with elevated gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> to detect a difference in a bioequivalence trial. This raises a concern, as demonstrated through simulation, that dissolution\/absorption differences in other formulations could be missed in routine bioequivalence trials. Aside from differences in active pharmaceutical ingredients (<jats:styled-content style=\"fixed-case\">API<\/jats:styled-content>s), other factors, such as changes in excipients or manufacturing methods, may also lead to exposure differences between formulations at elevated gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>. For formulations containing different forms of the same active moiety or the same <jats:styled-content style=\"fixed-case\">API<\/jats:styled-content> and showing different dissolution profiles at elevated <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> (i.e., <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> ~\u00a04\u20136.8), evaluation of bioequivalence with gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> modulators (e.g., a H<jats:sub>2<\/jats:sub> blocker) in addition to routine bioequivalence assessments may help to ensure therapeutic equivalence in patients with elevated gastric <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cts.12658","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T11:23:28Z","timestamp":1559820208000},"page":"564-572","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Proposal of Conducting Bioequivalence Trials with Gastric <scp>pH<\/scp> Modulators for Two Oral Formulations Demonstrating Different Dissolution Profiles at Elevated <scp>pH<\/scp>"],"prefix":"10.1111","volume":"12","author":[{"given":"Hao","family":"Zhu","sequence":"first","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Chen","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaning","family":"Wang","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramana S.","family":"Uppoor","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen","family":"Kuemmel","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehul","family":"Mehta","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology Office of Translational Science, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,16]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"US Food and Drug Administration 21 CFR320.1.Bioavailability and bioequivalence requirements [online]<https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=320.21>. Accessed May 3 2017."},{"key":"e_1_2_11_2_1","unstructured":"US Food and Drug Administration.Guidance for industry: bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA. [online] <https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm377465.pdf>. Accessed August 2 2017."},{"key":"e_1_2_11_3_1","unstructured":"US Food and Drug Administration.Guidance for industry: bioavailability and bioequivalence studies submitted in NDAs or INDs \u2013 general considerations. [online] <https:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm389370.pdf>. Accessed August 2 2017."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.02279.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.87"},{"key":"e_1_2_11_6_1","unstructured":"U.S. Package Insert of palbociclib. [online]. <https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/207103s004lbl.pdf>. 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