Translational Medicine-Scientific Operations, Novartis Healthcare Pvt Ltd, Hitech City, India.
J Clin Pharmacol. 2011 Jun;51(6):933-42. doi: 10.1177/0091270010376963. Epub 2010 Sep 17.
The steady-state pharmacokinetic (PK) interaction potential between amlodipine (10 mg), valsartan (320 mg), and hydrochlorothiazide (HCTZ; 25 mg) was evaluated in patients with hypertension in a multicenter, multiple-dose, open-label, 4-cohort, parallel-group study. Eligible patients were randomly allocated to the dual combination of valsartan + HCTZ, amlodipine + valsartan, or amlodipine + HCTZ and nonrandomly allotted to amlodipine + valsartan + HCTZ triple combination treatment. After 6 days of treatment with a half-maximal dose of different combinations, patients were up-titrated to the maximal drug doses from day 7 through day 17. PK parameters of corresponding analytes from the triple- and dual-treatment groups were estimated on day 17 and compared. Safety and tolerability of all treatments was assessed. The C ( ssmax ) and AUC(0-τ) values of amlodipine or HCTZ remained unaffected when administered with valsartan + HCTZ or valsartan + amlodipine, respectively. On the other hand, valsartan exposure increased by 10% to 25% when coadministered with HCTZ and amlodipine, which is not considered clinically relevant. In conclusion, there were no clinically relevant PK interactions with amlodipine, valsartan, and HCTZ triple combination compared with the corresponding dual combinations. All treatments were safe and well tolerated.
在一项多中心、多剂量、开放标签、4 队列、平行组研究中，评估了氨氯地平（10mg）、缬沙坦（320mg）和氢氯噻嗪（HCTZ；25mg）之间稳态药代动力学（PK）相互作用的潜力。符合条件的患者被随机分配到缬沙坦+ HCTZ、氨氯地平+缬沙坦或氨氯地平+ HCTZ 的双重组合治疗，而非随机分配到氨氯地平+缬沙坦+ HCTZ 的三联组合治疗。在接受不同组合半最大剂量治疗 6 天后，患者从第 7 天至第 17 天增加至最大药物剂量。在第 17 天，估计三重和双重治疗组中相应分析物的 PK 参数，并进行比较。评估了所有治疗的安全性和耐受性。当与缬沙坦+HCTZ 或缬沙坦+氨氯地平联合给药时，氨氯地平和 HCTZ 的 C（ssmax）和 AUC（0-τ）值保持不变。另一方面，当与 HCTZ 和氨氯地平联合给药时，缬沙坦的暴露量增加了 10%至 25%，这被认为没有临床意义。总之，与相应的双重组合相比，氨氯地平、缬沙坦和 HCTZ 三联组合没有临床相关的 PK 相互作用。所有治疗均安全且耐受良好。
