Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects

摘要

Objective: As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed. together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bio-equivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. Methods: This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 50 years with BMI between 18.5 and 25 kg/m(2). Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were C-max, AUC(last), and AUC(0-infinity), of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (Cis) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. Results: 60 subjects were enrolled and 55 completed the study. The 90% Cls of the geometric mean ratios of C-max, AUC(last), and AUC(0-infinity) were 0.9262 - 1.1498, 0.9294 - 1.0313, and 0.9312 - 1.0320 for telmisartan, 0.9041 - 1.0428, 0.9262 - 1.0085, and 0.9307 - 1.0094 for rosuvastatin, and 0.8718 - 1.0022, 0.8901 - 0.9904, and 0.8872 - 0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test treatments. Conclusions: Our findings suggest that the telmisartan/rosuvastatin FDC is bioequivalent to coadministration of separate tablets, and both treatments were safe and well tolerated. Administration of this FDC tablet is expected to improve patient compliance.