Effects of Hepatic Impairment on the Pharmacokinetic Profile and Safety of Lobeglitazone

Abstract

In this open‐label, single‐dose, parallel‐group study, we compared the pharmacokinetic profile and safety of lobeglitazone, a thiazolidinedione acting as an agonist for peroxisome proliferator‐activated receptors, in patients with hepatic impairment (HI) and healthy matched controls for age, sex, and body weight. After a single oral dose of lobeglitazone (0.5 mg), the lobeglitazone (parent drug) and M7 (major metabolite) plasma concentrations and pharmacokinetic parameters were analyzed and compared between the HI patient groups and healthy matched control groups. The geometric mean ratio (GMR; 90% confidence interval [CI]) for maximum concentration (Cmax) and area under the plasma concentration–time curve from time 0 extrapolated to infinity (AUCinf) of lobeglitazone was 1.06 (0.90‐1.24) and 1.07 (0.82‐1.40), respectively, for mild HI vs control A. The GMR (90%CI) of Cmax and AUCinf was 0.70 (0.56‐0.88) and 1.00 (0.72‐1.37), respectively, for moderate HI vs control B. For M7, the GMR (90%CI) of Cmax and AUCinf was 1.09 (0.75‐1.57) and 1.18 (0.71‐1.97), respectively, for mild HI vs control A and 1.50 (0.95‐2.38) and 1.79 (1.06‐3.04), respectively, for moderate HI vs control B. Notable adverse events or tolerability issues were not observed. Lobeglitazone may be safely used in patients with mild or moderate HI without dose adjustment.

Lobeglitazone and Its Therapeutic Benefits: A Review

“…The pharmacokinetic profile and safety of lobeglitazone were studied on T2DM patients with hepatic impairment compared with control groups. It was found that lobeglitazone can be safely prescribed to patients for T2DM with mild or moderate hepatic impairment without dose adjustment [23]. Generally, TZDs are related to various safety concerns such as weight gain.…”