Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. Issue 2 (19th August 2013)

• Record Type: Journal Article
• Authors: Macha, S.; Rose, P.; Mattheus, M.; Cinca, R.; Pinnetti, S.; Broedl, U. C.; Woerle, H. J.
• Is Part Of: Diabetes, obesity & metabolism. Volume 16:Issue 2(2014:Feb.)
• Page Start: 118
• Page End: 123
• Publication Date: 2013-08-19
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12183
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12183-abs-0001"> <title>Abstract</title> <sec id="dom12183-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12183-para-0001">This open‐label, parallel‐group study investigated the effect of various degrees of hepatic impairment on the pharmacokinetics, safety and tolerability of the sodium glucose cotransporter 2 inhibitor empagliflozin.</p> </sec> <sec id="dom12183-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12183-para-0002">Thirty‐six subjects [8 each with mild, moderate or severe hepatic impairment (Child–Pugh classification), and 12 matched controls with normal hepatic function] received a single 50 mg dose of empagliflozin.</p> </sec> <sec id="dom12183-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12183-para-0003">Empagliflozin was rapidly absorbed. After reaching peak levels, plasma drug concentrations declined in a biphasic fashion. Compared with subjects with normal hepatic function, geometric mean ratios (90% confidence interval) of AUC<sub>0</sub><sub>–∞</sub> and <italic>C</italic><sub>max</sub> were 123.15% (98.89–153.36) and 103.81% (82.29–130.95), respectively, in patients with mild hepatic impairment, 146.97% (118.02–183.02) and 123.31% (97.74–155.55), respectively, in patients with moderate hepatic impairment, and 174.70% (140.29–217.55) and 148.41% (117.65–187.23), respectively, in patients with severe hepatic impairment. Adverse events, all mild or moderate in intensity, were reported in three subjects with moderate hepatic impairment, two subjects with severe hepatic impairment and six subjects with normal hepatic function.</p> </sec> <sec id="dom12183-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12183-para-0004">Empagliflozin was well tolerated in subjects with hepatic impairment. Increases in empagliflozin exposure were less than twofold in patients with hepatic impairment; therefore no dose adjustment of empagliflozin is required in patients with hepatic impairment.</p> </sec> </abstract>