BACKGROUND: Probucol is indicated for primary hyperlipidemia and for hypercholesterolemia with hypertriglyceridemia. The objective of this study was to evaluate the tolerability and pharmacokinetics of probucol by multiple oral administration in healthy Korean male subjects. METHODS: This study was conducted by a randomized, openlabel, three-treatment, parallel-group design. A total of 30 subjects were randomly assigned to 1 of the 3 treatment groups were administered probucol orally at 250 mg once daily (QD) after breakfast (250 mg/d), at 500 mg once daily after breakfast (500 mg/d), or at 250 mg twice a day (b.i.d) after breakfast and dinner (500 mg/d) for 14 days. Serial samples of blood were collected and plasma drug concentrations were determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For tolerability assessment, measurement of vital signs and electrocardiograms (ECG), clinical laboratory tests and physical examinations were performed. RESULTS: At Day 13, the mean of the AUC(24h) of probucol was 123,800 µg × h/l in the 250 mg QD group, 198,500 µg × h/l in the 500 mg QD group, and 244,700 µg × h/l in the 250 mg BID group. The mean accumulation index for AUC(24h) (ratio of AUC(24h) for Day 13 to that for Day 1) was 2.5 in the 250 mg QD group, 2.85 in the 500 mg QD group, and 4.21 in the 250 mg b.i.d. group. No clinically significant changes in ECG, including QTc prolongation were observed during the study period. All adverse events were mild and no clinically significant changes were observed in any other tolerability assessment, thus confirming tolerability for all regimens tested. CONCLUSIONS: This study provided data on the pharmacokinetics and tolerability of probucol by multiple oral administrations in healthy male volunteers.