Pharmacokinetic Interaction Between Amlodipine and Lobeglitazone, a Novel Peroxisome Proliferator–activated Receptor-γ Agonist, in Healthy Subjects

Abstract

PurposeLobeglitazone, a peroxisome proliferator–activated receptor-γ agonist, was developed for the treatment of diabetes mellitus. Because the prevalence of hypertension is high among patients with diabetes mellitus, lobeglitazone is likely to be used with the antihypertensive drug amlodipine. We evaluated the pharmacokinetic interactions between lobeglitazone and amlodipine in healthy male Korean subjects. MethodsThe study used a randomized, open-label, multiple-dose, 3-treatment, 3-period, 6-sequence crossover design. A total of 24 healthy subjects were enrolled. Blood samples for pharmacokinetic analysis were collected according to a planned schedule after 0.5 mg of lobeglitazone and 10 mg of amlodipine were administered alone or concomitantly once per day for 10 days. FindingsA total of 24 healthy male subjects participated in the study (mean [SD] age, 26.6 [3.9] years; weight, 67.8 [5.7] kg; and height, 173.6 [6.4] cm). Three participants voluntarily withdrew after the second period, and 1 participant dropped out because of increased creatinine kinase levels caused by strenuous exercise before the start of the third period. Thus, 21 participants completed the study schedule to compare the pharmacokinetic parameters of lobeglitazone, and 22 participants completed the study of amlodipine. The geometric mean ratio (with 90% CIs) of Cmax,ss and AUCτ,ss for lobeglitazone administered concomitantly with amlodipine versus lobeglitazone administered alone was 1.01 (0.93–1.09) and 1.06 (0.92–1.23), respectively. The geometric mean ratio (with 90% CIs) of Cmax,ss and AUCτ,ss for amlodipine administered concomitantly with lobeglitazone versus amlodipine administered alone was 0.98 (0.94–1.02) and 1.00 (0.96–1.05). No serious drug-induced adverse events were reported in the study, and no clinically significant changes in vital signs, physical examination results, clinical laboratory results, or ECGs were noted. ImplicationsThe coadministration of lobeglitazone and amlodipine did not affect the pharmacokinetics of lobeglitazone or amlodipine in these healthy male Korean subjects. ClinicalTrials.gov identifier: NCT01341392.