title: Evaluation of pharmacokinetic interactions between amlodipine, valsartan, and hydrochlorothiazide in patients with hypertension.
abstract: 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.
authors.affiliation: Translational Medicine-Scientific Operations, Novartis Healthcare Pvt Ltd, Hitech City, India.
authors.forename: Prafulla
authors.initials: P
authors.lastname: Bhad
authors.forename: Surya
authors.initials: S
authors.lastname: Ayalasomayajula
authors.forename: Rajesh
authors.initials: R
authors.lastname: Karan
authors.forename: Selene
authors.initials: S
authors.lastname: Leon
authors.forename: Gillies-Jacques
authors.initials: GJ
authors.lastname: Riviere
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sunkara
authors.forename: Venkateswar
authors.initials: V
authors.lastname: Jarugula
mesh_terms: D000293:Adolescent; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068756:Valsartan
chemical_list: D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents; D004338:Drug Combinations; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine