<p>Naproxen is heavily metabolized in the liver and undergoes both Phase I and Phase II metabolism.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Naprelan FDA Label" href="#reference-L6582">12</a></sup><sup class="text-reference-group"><a class="reference-popover-link" data-content="Naprosyn FDA Label" href="#reference-L6583">13</a></sup><sup class="text-reference-group"><a class="reference-popover-link" data-content="Falany CN, Strom P, Swedmark S: Sulphation of o-desmethylnaproxen and related compounds by human cytosolic sulfotransferases. Br J Clin Pharmacol. 2005 Dec;60(6):632-40. doi: 10.1111/j.1365-2125.2005.02506.x. (PubMed ID 16305588)" href="#reference-A179197">7</a></sup> The first step involves demethylation of naproxen via CYP 1A2, 2C8, and 2C9<sup class="text-reference-group"><a class="reference-popover-link" data-content="Bowalgaha K, Elliot DJ, Mackenzie PI, Knights KM, Swedmark S, Miners JO: S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33. doi: 10.1111/j.1365-2125.2005.02446.x. (PubMed ID 16187975)" href="#reference-A179191">8</a></sup><sup class="text-reference-group"><a class="reference-popover-link" data-content="Tracy TS, Marra C, Wrighton SA, Gonzalez FJ, Korzekwa KR: Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol. 1997;52(4):293-8. (PubMed ID 9248768)" href="#reference-A38985">9</a></sup>. Both naproxen and desmethylnaproxen proceed to Phase II metabolism; however, desmethylnaproxen can form both acyl and phenolic glucoronide products, while naproxen only produces the acyl glucuronide.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Bowalgaha K, Elliot DJ, Mackenzie PI, Knights KM, Swedmark S, Miners JO: S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33. doi: 10.1111/j.1365-2125.2005.02446.x. (PubMed ID 16187975)" href="#reference-A179191">8</a></sup><sup class="text-reference-group"><a class="reference-popover-link" data-content="Falany CN, Strom P, Swedmark S: Sulphation of o-desmethylnaproxen and related compounds by human cytosolic sulfotransferases. Br J Clin Pharmacol. 2005 Dec;60(6):632-40. doi: 10.1111/j.1365-2125.2005.02506.x. (PubMed ID 16305588)" href="#reference-A179197">7</a></sup> The acyl glucuronidation process involves UGT 1A1, 1A3, 1A6, 1A7, 1A9, 1A10 and 2B7, while phenolic glucuronidation is catalyzed by UGT 1A1, 1A7,1A9, and 1A10.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Bowalgaha K, Elliot DJ, Mackenzie PI, Knights KM, Swedmark S, Miners JO: S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33. doi: 10.1111/j.1365-2125.2005.02446.x. (PubMed ID 16187975)" href="#reference-A179191">8</a></sup> Desmethylnaproxen also undergoes sulphation which is mediated by SULT 1A1, 1B1 and 1E1.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Falany CN, Strom P, Swedmark S: Sulphation of o-desmethylnaproxen and related compounds by human cytosolic sulfotransferases. Br J Clin Pharmacol. 2005 Dec;60(6):632-40. doi: 10.1111/j.1365-2125.2005.02506.x. (PubMed ID 16305588)" href="#reference-A179197">7</a></sup></p><p class="d-none d-sm-block"><strong>Hover over products below to view reaction partners</strong></p>