PDF(Pubmed)
Abstract：
UNASSIGNED: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA).
UNASSIGNED: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study.
UNASSIGNED: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects.
UNASSIGNED: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.
UNASSIGNED: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study.
UNASSIGNED: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects.
UNASSIGNED: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.
摘要：
■高血压和高脂血症的管理，这是心血管疾病常见的共病危险因素，需要多种药物。含有依泽替米贝的固定剂量组合（FDC）的开发，瑞舒伐他汀,替米沙坦,氨氯地平旨在提高患者的依从性和持久性，但是四种药物之间的潜在相互作用尚未被研究。本研究旨在评估依泽替米贝/瑞舒伐他汀10/20mg（ER）的FDC与替米沙坦/氨氯地平80/5mg（TA）的FDC之间的药代动力学（PK）相互作用。
■开放标签，单序列，三个时期，在健康男性受试者中进行了三治疗交叉研究.所有受试者接受ER7天，在每个治疗期间,TA持续9天,ER与TA联合持续7天。对于总/游离依泽替米贝的PK分析，瑞舒伐他汀,替米沙坦,和氨氯地平,在稳态下连续收集血液样品24小时。在整个研究中评估安全性概况。
■共招募了38名受试者，34名受试者完成了这项研究。两种FDC共同施用后对每种活性成分的全身暴露与每种FDC单独施用后的全身暴露相似。联合治疗与单一治疗的最大血浆浓度（µg/L）和血浆浓度-时间曲线下面积（h·µg/L）的几何平均比率和90％置信区间，在稳定状态下评估，如下：总依泽替米贝，1.0264（0.8765-1.2017）和0.9359（0.7847-1.1163）；免费依泽替米贝，1.5713（1.2821-1.9257）和0.9941（0.8384-1.1788）；瑞舒伐他汀，2.1673（1.7807-2.6379）和1.1714（0.9992-1.3733）；替米沙坦，1.0745（0.8139-1.4186）和1.1057（0.8379-1.4591）；和氨氯地平，0.9421（0.8764-1.0126）和0.9603（0.8862-1.0405）。组合疗法和单一疗法均被受试者良好耐受。
■依泽替米贝/瑞舒伐他汀10/20mg和依泽替米贝/瑞舒伐他汀10/20mg联合给药在健康受试者中耐受性良好，这两种FDC之间的PK相互作用没有临床意义。
■开放标签，单序列，三个时期，在健康男性受试者中进行了三治疗交叉研究.所有受试者接受ER7天，在每个治疗期间,TA持续9天,ER与TA联合持续7天。对于总/游离依泽替米贝的PK分析，瑞舒伐他汀,替米沙坦,和氨氯地平,在稳态下连续收集血液样品24小时。在整个研究中评估安全性概况。
■共招募了38名受试者，34名受试者完成了这项研究。两种FDC共同施用后对每种活性成分的全身暴露与每种FDC单独施用后的全身暴露相似。联合治疗与单一治疗的最大血浆浓度（µg/L）和血浆浓度-时间曲线下面积（h·µg/L）的几何平均比率和90％置信区间，在稳定状态下评估，如下：总依泽替米贝，1.0264（0.8765-1.2017）和0.9359（0.7847-1.1163）；免费依泽替米贝，1.5713（1.2821-1.9257）和0.9941（0.8384-1.1788）；瑞舒伐他汀，2.1673（1.7807-2.6379）和1.1714（0.9992-1.3733）；替米沙坦，1.0745（0.8139-1.4186）和1.1057（0.8379-1.4591）；和氨氯地平，0.9421（0.8764-1.0126）和0.9603（0.8862-1.0405）。组合疗法和单一疗法均被受试者良好耐受。
■依泽替米贝/瑞舒伐他汀10/20mg和依泽替米贝/瑞舒伐他汀10/20mg联合给药在健康受试者中耐受性良好，这两种FDC之间的PK相互作用没有临床意义。
