{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:12:36Z","timestamp":1787717556068,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Little is known about the course of the plasma concentration and the bioavailability of non\u2010steroidal anti\u2010inflammatory drugs (<jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>s) contained in dermal patches. We compared an etofenamate prototype patch (patent <jats:styled-content style=\"fixed-case\">EP<\/jats:styled-content> 1833471) and a commercially available diclofenac epolamine patch regarding the bioavailability of the active ingredients relative to respective i.m. applications and regarding their plasma concentration\u2013time course. Twenty\u2010four healthy human volunteers were treated using a parallel group design (n = 12 per group) with a single dermal patch (removed after 12 hr) followed (after a latency of 48 hr) by eight consecutive dermal patches every 12 hr to reach steady\u2010state conditions. The patches were generally well tolerated, but one volunteer treated with etofenamate developed an allergic contact dermatitis. After the first patch, <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> was 0.81 \u00b1 0.11 (mean \u00b1 <jats:styled-content style=\"fixed-case\">S.E.M.<\/jats:styled-content>) ng\/mL (reached 12 hr after patch removal) for diclofenac and 31.3 \u00b1 3.8 ng\/mL for flufenamic acid (reached at patch removal), the main metabolite of etofenamate. Etofenamate was not detectable. After repetitive dosing, trough plasma concentrations after the eighth dose were 1.72 \u00b1 0.32 ng\/mL for diclofenac and 48.7 \u00b1 6.6 ng\/mL for flufenamic acid. Bioavailabilities (single dose) relative to i.m. applications were 0.22 \u00b1 0.04% for diclofenac and 1.15 \u00b1 0.06% for flufenamic acid. In conclusion, the relative bioavailability (compared to the respective i.m. application) of both drugs is low. The maximal plasma concentrations after topical administration of these drugs are well below the <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> values for <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20101 and <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102, explaining the absence of dose\u2010dependent toxicities.<\/jats:p>","DOI":"10.1111\/bcpt.12818","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T12:27:05Z","timestamp":1496233625000},"page":"423-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacokinetics of Transdermal Etofenamate and Diclofenac in Healthy Volunteers"],"prefix":"10.1111","volume":"121","author":[{"given":"Sara","family":"Drago","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology University Hospital Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Imboden","sequence":"additional","affiliation":[{"name":"Drossapharm Ltd. Basel\/Arlesheim Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schlatter","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology University Hospital Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirabel","family":"Buylaert","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology University Hospital Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kr\u00e4henb\u00fchl","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology University Hospital Basel Switzerland"},{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Drewe","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology University Hospital Basel Switzerland"},{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60900-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198403013100905"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c7086"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199906173402407"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmig.2006.02.001"},{"key":"e_1_2_6_7_1","first-page":"193","article-title":"Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double\u2010blind, controlled clinical trial","volume":"21","author":"Br\u00fchlmann P","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02484.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042752-200307000-00002"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)63324-7"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.1995.tb09874.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200060030-00004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2008.03.006"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00568201"},{"key":"e_1_2_6_15_1","first-page":"1322","article-title":"On biochemistry and pharmacokinetics of etofenamate\/studies in man","volume":"27","author":"Dell HD","year":"1977","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_6_16_1","first-page":"9","article-title":"Metabolism of etofenamate\/Identification and analytic of metabolites, their pharmacological properties and species dependence of metabolism","volume":"31","author":"Dell HD","year":"1981","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_6_17_1","first-page":"1487","article-title":"Plasma\u2010 und Gewebespiegel\u2010Studien nach intramuskul\u00e4rer Applikation von Etofenamate. 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