<p>Diltiazem is subject to extensive first-pass metabolism, which explains its relatively low absolute oral bioavailability. It undergoes N-demethylation primarily mediated by CYP3A4. CYP2D6 is responsible for O-demethylation and esterases mediate deacetylation.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Molden E, Asberg A, Christensen H: Desacetyl-diltiazem displays severalfold higher affinity to CYP2D6 compared with CYP3A4. Drug Metab Dispos. 2002 Jan;30(1):1-3. (PubMed ID 11744603)" href="#reference-A39292">7</a></sup> There was large inter-individual variability in the circulating plasma levels of metabolites in healthy volunteers.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Yeung PK, Prescott C, Haddad C, Montague TJ, McGregor C, Quilliam MA, Xei M, Li R, Farmer P, Klassen GA: Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. Eur J Drug Metab Pharmacokinet. 1993 Apr-Jun;18(2):199-206. doi: 10.1007/BF03188796. (PubMed ID 8243504)" href="#reference-A178516">6</a></sup></p><p>In healthy volunteers, the major circulating metabolites in the plasma are N-monodesmethyl diltilazem, deacetyl diltiazem, and deacetyl N-monodesmethyl diltiazem, which are all pharmacologically active.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Yeung PK, Prescott C, Haddad C, Montague TJ, McGregor C, Quilliam MA, Xei M, Li R, Farmer P, Klassen GA: Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. Eur J Drug Metab Pharmacokinet. 1993 Apr-Jun;18(2):199-206. doi: 10.1007/BF03188796. (PubMed ID 8243504)" href="#reference-A178516">6</a></sup> Deacetyl diltiazem retains about 25-50% of the pharmacological activity to that of the parent compound.<sup class="text-reference-group"><a class="reference-popover-link" data-content="CARDIZEM® LA (diltiazem hydrochloride) extended-release tablets - FDA Label" href="#reference-L10556">12</a></sup> Deacetyl diltiazem can be further transformed into deacetyl diltiazem N-oxide or deacetyl O-desmethyl diltiazem. N-monodesmethyl diltilazem can be further metabolized to N,O-didesmethyl diltiazem. Deacetyl N-monodesmethyl diltiazem can be further metabolized to deacetyl N,O-didesmethyl diltiazem, which can be glucuronidated or sulphated.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Yeung PK, Prescott C, Haddad C, Montague TJ, McGregor C, Quilliam MA, Xei M, Li R, Farmer P, Klassen GA: Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. Eur J Drug Metab Pharmacokinet. 1993 Apr-Jun;18(2):199-206. doi: 10.1007/BF03188796. (PubMed ID 8243504)" href="#reference-A178516">6</a></sup> Diltiazem can be O-demethylated by CYP2D6 to form O-desmethyl diltiazem.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Molden E, Asberg A, Christensen H: Desacetyl-diltiazem displays severalfold higher affinity to CYP2D6 compared with CYP3A4. Drug Metab Dispos. 2002 Jan;30(1):1-3. (PubMed ID 11744603)" href="#reference-A39292">7</a></sup></p><p class="d-none d-sm-block"><strong>Hover over products below to view reaction partners</strong></p>