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Purpose: Lobeglitazone, a peroxisome proliferatoractivated receptor-γ agonist, is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. Individuals concomitantly taking lobeglitazone and a CYP3A4 inhibitor may experience some adverse effects secondary to increased systemic exposure to lobeglitazone. To address such potential concern, we evaluated the effects of ketoconazole, a prototypic CYP3A4 inhibitor, on the pharmacokinetic (PK) properties and associated adverse effects of lobeglitazone. Methods: A PK drug-drug interaction study was conducted in healthy individuals between 20 and 45 years old in a randomized, open-label, 2-way crossover design. Even though the PK study was performed on a single dose of lobeglitazone, multiple ketoconazole doses were given to ensure that the full extent of inhibition of CYP3A4 was maintained during the PK sampling. All study participants received a single oral dose of lobeglitazone 0.5 mg with or without 9 oral 200-mg doses of ketoconazole pretreatment twice daily. The primary PK parameter end points (AUC and Cmax) were estimated using noncompartmental analysis, and the 90% CIs for the geometric mean ratios (ratio of lobeglitazone and ketoconazole to lobeglitazone alone) were investigated. Tolerability (adverse events, vital signs, ECG, and laboratory tests) was also assessed. Findings: A total of 24 Korean men (mean age, 26 years; age range, 20-32 years; mean weight, 68 kg; weight range, 59-81 kg) completed the study and were evaluable for lobeglitazone PK properties and tolerability. The mean (SD) Cmax values of lobeglitazone with and without ketoconazole were 49 (7) ng/mL and 48 (6) ng/mL at 1.5 and 1.0 hours after dosing, respectively. The mean (SD) AUC∞ values were 532 (117) ng · h/mL and 405 (110) ng · h/mL, respectively. Although the Cmax was not significantly affected, the geometric mean ratio for AUAUC∞ was increased by a point estimate of 1.33 (90% CI, 1.23-1.44). A single oral administration of lobeglitazone 0.5 mg with or without ketoconazole pretreatment did not produce any clinically significant adverse effects on vital signs, 12-lead ECG profiles, or laboratory tests. Implications: The administration of lobeglitazone, 0.5 mg alone or in combination with multiple doses of ketoconazole, was generally well tolerated. The systemic exposure of lobeglitazone was increased to a modest extent by pretreatment with 9 twicedaily doses of ketoconazole. [ABSTRACT FROM AUTHOR]