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首页> 外文期刊>Drug Design, Development and Therapy >Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects
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Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects

机译：健康韩国男性受试者多次口服给药后，替米沙坦/氨氯地平与瑞舒伐他汀之间的药代动力学相互作用

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Purpose: Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers. Patients and methods: An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80?mg/5?mg once daily for 14?days with or without one tablet of rosuvastatin 20?mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20?mg once daily for 14?days with or without one tablet of telmisartan/amlodipine 80?mg/5?mg once daily. Serial blood samples were collected up to 24?hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Csubmax,ss/sub) and area under the plasma concentration versus time curve over dosing interval (AUCsubτ,ss/sub), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Csubmax,ss/sub and AUCsubτ,ss/sub for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions. Results: Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Csubmax,ss/sub and AUCsubτ,ss,/sub were 0.9829 (0.8334–1.1590) and 1.0003 (0.9342–1.0710) for telmisartan; 0.9908 (0.9602–1.0223) and 1.0081 (0.9758–1.0413) for amlodipine; and 2.2762 (2.0113–2.5758) and 1.3261 (1.2385–1.4198) for rosuvastatin, respectively. Conclusion: The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.
机译：目的：高血压和血脂异常是心血管疾病的主要危险因素，可以通过将降压药与他汀类药物联合使用来降低心血管疾病的风险。这项研究的目的是评估替米沙坦/氨氯地平固定剂量组合与瑞舒伐他汀在健康的韩国男性志愿者中的药代动力学相互作用。患者和方法：在健康男性受试者中进行了一项开放标签，两队列，多剂量，单序列的交叉研究。在第1组中，受试者每天服用1片替米沙坦/氨氯地平80？mg / 5？mg每天一次，持续14？天，每天是否服用1片瑞舒伐他汀20？mg。在第2组中，受试者每天服用1片瑞舒伐他汀20毫克（毫克），持续14天内，每天或不服用1片替米沙坦/氨氯地平80毫克/ 5毫克（每天）。在第1组第9天和第14天以及在第2组第5天和第14天，在服药后24小时内收集连续血样。通过液相色谱/串联质谱法测量血浆药物浓度。药代动力学参数包括稳态最大血浆浓度（C max，ss ）和在给药间隔内血浆浓度与时间曲线下面积（AUC τ，ss ）通过非房室分析确定。分别或并发对数转换后的C max，ss 和AUC τ，ss 的几何最小二乘均值（GLSM）比率和相关的90％置信区间（CIs）计算疗法以评估药代动力学相互作用。结果：队列1的38名受试者和队列2的19名受试者完成了研究。替米沙坦的C ss 和AUC τ，ss 的GLSM比率和90％CI分别为0.9829（0.8334–1.1590）和1.0003（0.9342–1.0710）。氨氯地平为0.9908（0.9602-1.0223）和1.0081（0.9758-1.0413）;罗苏伐他汀分别为2.2762（2.0113-2.5758）和1.3261（1.2385-1.4198）。结论：替米沙坦/氨氯地平的药代动力学参数符合罗格列汀的等效标准，但不是瑞舒伐他汀。在实践中，替米沙坦/氨氯地平共同给药引起的瑞舒伐他汀全身暴露量的增加在临床上不会有重大意义。尽管如此，仍需要适当设计的两序列交叉研究来确认这项研究的结果。

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