Evaluation of Pharmacokinetic Interactions Between Amlodipine, Valsartan, and Hydrochlorothiazide in Patients With Hypertension

Authors

  • Mr Prafulla Bhad MPharm,

    1. Translational Medicine-Scientific Operations, Novartis Healthcare Pvt Ltd, Hitech City, India
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  • Dr Surya Ayalasomayajula PhD,

    Corresponding author
    1. TS-DMPK-Clinical PK/PD, Novartis Institutes of Biomedical Research, East Hanover, New Jersey
      Address for correspondence: Surya Ayalasomayajula, Novartis Institutes for Biomedical Research, Translational Sciences-DMPK-GPK/PD, One Health Plaza, Bldg 438/3413C, East Hanover, NJ 07936; e-mail: surya.ayalasomayajula@novartis.com.
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  • Dr Rajesh Karan DM,

    1. Translational Medicine-Scientific Operations, Novartis Healthcare Pvt Ltd, Hitech City, India
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  • Dr Selene Leon PhD,

    1. Clinical Information Sciences, Novartis Institutes of Biomedical Research, East Hanover, New Jersey
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  • Dr Gillies-Jacques Riviere PhD,

    1. Drug Metabolism and Bioanalytics, Novartis Pharma AG, Basel, Switzerland
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  • Dr Gangadhar Sunkara PhD,

    1. TS-DMPK-Clinical PK/PD, Novartis Institutes of Biomedical Research, East Hanover, New Jersey
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  • Dr Venkateswar Jarugula PhD

    1. TS-DMPK-Clinical PK/PD, Novartis Institutes of Biomedical Research, East Hanover, New Jersey
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Address for correspondence: Surya Ayalasomayajula, Novartis Institutes for Biomedical Research, Translational Sciences-DMPK-GPK/PD, One Health Plaza, Bldg 438/3413C, East Hanover, NJ 07936; e-mail: surya.ayalasomayajula@novartis.com.

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 Cssmax and AUC0-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.

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