<p>Lovastatin Cmax was found to be 3.013ng/mL with a Tmax of 3.36 hours.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Health Canada Monograph - Lovastatin" href="#reference-F4664">44</a></sup></p><p>Plasma concentrations of total radioactivity (lovastatin plus 14C-metabolites) peaked at 2 hours and declined rapidly to about 10% of peak by 24 hours postdose. Absorption of lovastatin, estimated relative to an intravenous reference dose, in each of four animal species tested, averaged about 30% of an oral dose. In animal studies, after oral dosing, lovastatin had high selectivity for the liver, where it achieved substantially higher concentrations than in non-target tissues. Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. As a consequence of extensive hepatic extraction of lovastatin, the availability of drug to the general circulation is low and variable. In a single dose study in four hypercholesterolemic patients, it was estimated that less than 5% of an oral dose of lovastatin reaches the general circulation as active inhibitors. Following administration of lovastatin tablets the coefficient of variation, based on between-subject variability, was approximately 40% for the area under the curve (AUC) of total inhibitory activity in the general circulation.<sup class="text-reference-group"><a class="reference-popover-link" data-content="FDA Label - Lovastatin" href="#reference-F4661">43</a>,<a class="reference-popover-link" data-content="Health Canada Monograph - Lovastatin" href="#reference-F4664">44</a></sup></p><p>The peak concentrations of lovastatin when a dose of 10-40 mg is administered are reported to range from 1.04-4.03 ng/ml and an AUC of 14-53 ng.h/ml. This indicates that lovastatin presents a dose-dependent pharmacokinetic profile.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Lamson M, Phillips G, Shen J, Lukacsko P, Friedhoff L, Niecestro RM: Pharmacokinetics of lovastatin extended-release dosage form (Lovastatin XL) in healthy volunteers. Biopharm Drug Dispos. 2002 May;23(4):143-9. doi: 10.1002/bdd.304. (PubMed ID 12015788)" href="#reference-A174586">8</a></sup> When lovastatin was given under fasting conditions, plasma concentrations of both active and total inhibitors were on average about two-thirds those found when lovastatin was administered immediately after a standard test meal.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Health Canada Monograph - Lovastatin" href="#reference-F4664">44</a></sup></p><p>Genetic differences in the OATP1B1 (Organic-Anion-Transporting Polypeptide 1B1) hepatic transporter encoded by the SCLCO1B1 gene (Solute Carrier Organic Anion Transporter family member 1B1) have been shown to impact lovastatin pharmacokinetics.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Zhao G, Liu M, Wu X, Li G, Qiu F, Gu J, Zhao L: Effect of polymorphisms in CYP3A4, PPARA, NR1I2, NFKB1, ABCG2 and SLCO1B1 on the pharmacokinetics of lovastatin in healthy Chinese volunteers. Pharmacogenomics. 2017 Jan;18(1):65-75. doi: 10.2217/pgs.16.31. Epub 2016 Dec 14. (PubMed ID 27967318)" href="#reference-A181943">34</a></sup> Evidence from pharmacogenetic studies of the c.521T&gt;C single nucleotide polymorphism (SNP) showed that lovastatin Cmax and AUC were 340 and 286% higher, respectively, for individuals homozygous for 521CC compared to homozygous 521TT individuals.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Tornio A, Vakkilainen J, Neuvonen M, Backman JT, Neuvonen PJ, Niemi M: SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid. Pharmacogenet Genomics. 2015 Aug;25(8):382-7. doi: 10.1097/FPC.0000000000000148. (PubMed ID 26020121)" href="#reference-A181946">35</a></sup> The 521CC genotype is also associated with a marked increase in the risk of developing myopathy, likely secondary to increased systemic exposure.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Xiang Q, Chen SQ, Ma LY, Hu K, Zhang Z, Mu GY, Xie QF, Zhang XD, Cui YM: Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis. Pharmacogenomics J. 2018 Dec;18(6):721-729. doi: 10.1038/s41397-018-0054-0. Epub 2018 Sep 24. (PubMed ID 30250148)" href="#reference-A181955">36</a></sup> Other statin drugs impacted by this polymorphism include <a href="https://go.drugbank.com/drugs/DB01098">rosuvastatin</a>, <a href="https://go.drugbank.com/drugs/DB08860">pitavastatin</a>, <a href="https://go.drugbank.com/drugs/DB01076">atorvastatin</a>, <a href="https://go.drugbank.com/drugs/DB00641">simvastatin</a>, and <a href="https://go.drugbank.com/drugs/DB00175">pravastatin</a>.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Elsby R, Hilgendorf C, Fenner K: Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012 Nov;92(5):584-98. doi: 10.1038/clpt.2012.163. Epub 2012 Oct 10. (PubMed ID 23047648)" href="#reference-A181460">28</a></sup></p><p>While specific dosage instructions are not included in the available product monographs for lovastatin, individuals with the above-mentioned c.521CC OATP1B1 genotype should be monitored for development of adverse effects from increased exposure to the drug, such as muscle pain and risk of rhabdomyolysis, particularly at higher doses.</p>