Effect of High-Fat Food on the Pharmacokinetics and Safety of Amlodipine/Benazepril in Healthy Chinese Participants

Clin Pharmacol Drug Dev. 2026 Jan;15(1):e70022. doi: 10.1002/cpdd.70022.

Abstract

This study assessed the effect of high-fat food on pharmacokinetics and safety of amlodipine, benazepril, and benazeprilat in healthy Chinese participants under fasting and fed conditions from a bioequivalence trial. This trial enrolled a total of 92 healthy participants, and there was a significant difference in age between fasting and fed trials (P = .006). These participants received an amlodipine/benazepril capsule containing 5 mg amlodipine and 10 mg benazepril each period with a 21-day washout under fasting or fed conditions. Twenty-four blood samples were obtained from baseline to 168 h after drug administration for pharmacokinetic analyses. The plasma concentrations of amlodipine, benazepril, and benazeprilat were determined by a validated liquid chromatography-tandem mass spectrometry method. After controlling for age, analysis of covariance (ANCOVA) or Quade's ANCOVA of pharmacokinetic results indicated that a high-fat meal did not significantly influence the primary pharmacokinetic parameters of amlodipine, benazepril, and benazeprilat, except for the maximum plasma concentration (Cmax) and time to reach maximum plasma concentration (Tmax) for benazepril and benazeprilat. The high-fat food decreased Cmax of benazepril by 64.1% and Cmax of benazeprilat by 30.8%, and increased Tmax of benazepril by 408.2% and Tmax of benazeprilat by 167.8% The incidence of most frequently observed AE of hypotension was significantly different (P = .014, risk ratio = 2.286, and 95% confidence intervals 1.103 to 4.737) under fasting and fed conditions. It suggested that high-fat food containing 800 to 1000 kcal might be the risk factor for healthy Chinese participants taking amlodipine/benazepril capsules.

Keywords: amlodipine; benazepril; benazeprilat; high‐fat food; pharmacokinetic.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amlodipine* / administration & dosage
  • Amlodipine* / adverse effects
  • Amlodipine* / blood
  • Amlodipine* / pharmacokinetics
  • Benzazepines* / administration & dosage
  • Benzazepines* / adverse effects
  • Benzazepines* / blood
  • Benzazepines* / pharmacokinetics
  • Calcium Channel Blockers* / administration & dosage
  • Calcium Channel Blockers* / adverse effects
  • Calcium Channel Blockers* / pharmacokinetics
  • Cross-Over Studies
  • Diet, High-Fat* / adverse effects
  • Drug Combinations
  • East Asian People
  • Fasting
  • Female
  • Food-Drug Interactions*
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Amlodipine
  • benazepril
  • Benzazepines
  • Calcium Channel Blockers
  • Drug Combinations

Supplementary concepts

  • Chinese people