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Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment.
Diabetes Obes Metab. 2014 Feb; 16(2):118-23.DO

Abstract

AIMS

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.

METHODS

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.

RESULTS

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(0-∞) and C(max) 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.

CONCLUSIONS

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.

Authors+Show Affiliations

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23859534

Citation

Macha, S, et al. "Pharmacokinetics, Safety and Tolerability of Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, in Patients With Hepatic Impairment." Diabetes, Obesity & Metabolism, vol. 16, no. 2, 2014, pp. 118-23.
Macha S, Rose P, Mattheus M, et al. Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. Diabetes Obes Metab. 2014;16(2):118-23.
Macha, S., Rose, P., Mattheus, M., Cinca, R., Pinnetti, S., Broedl, U. C., & Woerle, H. J. (2014). Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. Diabetes, Obesity & Metabolism, 16(2), 118-23. https://doi.org/10.1111/dom.12183
Macha S, et al. Pharmacokinetics, Safety and Tolerability of Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, in Patients With Hepatic Impairment. Diabetes Obes Metab. 2014;16(2):118-23. PubMed PMID: 23859534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment. AU - Macha,S, AU - Rose,P, AU - Mattheus,M, AU - Cinca,R, AU - Pinnetti,S, AU - Broedl,U C, AU - Woerle,H J, Y1 - 2013/08/19/ PY - 2013/01/21/received PY - 2013/02/28/revised PY - 2013/07/11/accepted PY - 2013/7/18/entrez PY - 2013/7/19/pubmed PY - 2015/5/13/medline KW - BI 10773 KW - empagliflozin KW - hepatic impairment KW - pharmacokinetics KW - sodium glucose cotransporter 2 inhibitor SP - 118 EP - 23 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 16 IS - 2 N2 - AIMS: 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. METHODS: 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. RESULTS: 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(0-∞) and C(max) 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. CONCLUSIONS: 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. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/23859534/Pharmacokinetics_safety_and_tolerability_of_empagliflozin_a_sodium_glucose_cotransporter_2_inhibitor_in_patients_with_hepatic_impairment_ L2 - https://doi.org/10.1111/dom.12183 DB - PRIME DP - Unbound Medicine ER -