Premium
Evaluation of Pharmacokinetic Interactions Between Amlodipine, Valsartan, and Hydrochlorothiazide in Patients With Hypertension
Author(s) -
Bhad Prafulla,
Ayalasomayajula Surya,
Karan Rajesh,
Leon Selene,
Riviere GilliesJacques,
Sunkara Gangadhar,
Jarugula Venkateswar
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010376963
Subject(s) - amlodipine , valsartan , hydrochlorothiazide , medicine , pharmacology , tolerability , pharmacokinetics , urology , adverse effect , blood pressure
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.