Chae Dong Woo, Son Mijeong, Kim Yukyung, Son Hankil, Jang Seong Bok, Seo Jeong Min, Nam Su Youn, Park Kyungsoo
Int J Clin Pharmacol Ther. 2015 Oct;53(10):883-9. doi: 10.5414/CP202412.
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 bioequivalence 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.
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/m2. 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 Cmax, AUClast, and AUC0-∞ 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.
60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ 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.
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.
由于高血压和血脂异常常合并存在，抗高血压药物和降脂药物常联合使用进行治疗。替米沙坦和瑞舒伐他汀广泛联合用于治疗高血压和血脂异常。这两种药物的复方制剂因给药方便可提高患者依从性。本研究的目的是评估在健康韩国男性志愿者中，单剂量给予新开发的含替米沙坦/瑞舒伐他汀80/20 mg的固定剂量复方（FDC）片剂（试验治疗）与分别给予80 mg替米沙坦片和20 mg瑞舒伐他汀片（参比治疗）的生物等效性。
这是一项单剂量、随机、开放标签、两周期交叉研究，纳入年龄在20 - 50岁、BMI在18.5至25 kg/m²之间的健康男性。每位受试者接受单剂量的参比治疗和试验治疗，洗脱期为14天。给药后长达72小时内按预定时间间隔进行血样采集。主要药代动力学参数为替米沙坦、瑞舒伐他汀和N - 去甲基瑞舒伐他汀的Cmax、AUClast和AUC0 - ∞。通过确定这些参数的几何平均比值（试验治疗/参比治疗）的90%置信区间（CI）是否在80%至125%的标准范围内来评估生物等效性。通过定期与受试者访谈和体格检查监测不良事件。
共纳入60名受试者，55名完成研究。替米沙坦的Cmax、AUClast和AUC0 - ∞的几何平均比值的90%CI分别为0.9262 - 1.1498、0.9294 - 1.0313和0.9312 - 1.0320；瑞舒伐他汀的分别为0.9041 - 1.0428、0.9262 - 1.0085和0.9307 - 1.0094；N - 去甲基瑞舒伐他汀的分别为0.8718 - 1.0022、0.8901 - 0.9904和0.8872 - 0.9767。参比治疗和试验治疗之间不良事件（均为轻度或中度）的发生率无统计学差异。
我们的研究结果表明，替米沙坦/瑞舒伐他汀FDC与分别给药片剂具有生物等效性，且两种治疗均安全且耐受性良好。预计给予这种FDC片剂可提高患者依从性。
