S-amlodipine–bisoprolol combination therapy caused elevated transaminases and triglyceride levels in healthy Chinese subjects: a randomized controlled, open-label, multiple-dose pharmacokinetic interaction study

ABSTRACT

Introduction: S-amlodipine is main anti-hypertensive active enantiomer of amlodipine. Bisoprolol is a β-blocker particularly suitable for hypertensive patients with sinus tachycardia. We evaluated the pharmacokinetic interaction between S-amlodipine and bisoprolol in healthy Chinese subjects.

Areas covered: Thirty-two subjects were randomly divided into two equal groups. Subjects in group A were administered S-amlodipine 5 mg for 10 days followed by S-amlodipine 5 mg plus bisoprolol 5 mg for 7 days. Subjects in group B were administered bisoprolol 5 mg for 7 days, followed by S-amlodipine 5 mg plus bisoprolol 5 mg for 10 days. Blood samples were collected for evaluation of pharmacokinetic interaction. Tolerability was evaluated by interview, vital signs, 12-lead ECGs, physical examination, and clinical laboratory tests.

Expert opinion: The geometric mean ratio (90% CI) for amlodipine AUC_τ,ss and C_ss-max during the monotherapy and combination therapy periods were 1.0389 (0.9879, 1.0926) and 1.0213 (0.9556, 1.0915). For bisoprolol, it was 1.0193 (0.9834, 1.0566) and 0.9989 (0.9133, 1.0925). Most adverse events were mild-moderate. There was high incidence of elevated alanine aminotransferase, aspartate aminotransferase, and triglyceride.This study found no pharmacokinetic interaction between S-amlodipine and bisoprolol. Alanine aminotransferase, aspartate aminotransferase, and triglycerides should be closely monitored.

KEYWORDS:

• Hypertension
• amlodipine
• bisoprolol
• pharmacokinetic interaction
• transaminases elevation

Author contributions

J. Liu, X. Li, Y. Liu, M. Wu, J. Niu and Y. Ding conducted the clinical trial. H. Zhang participated in statistical analysis of the collected data. J. Liu prepared the manuscript. All authors reviewed the results and approved the final version of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was financially supported by the National Major Scientific and Technological Special Project for ‘Significant New Drug Development’ during the Twelfth Five-Year Planning Period of China [Project: 2014ZX09303303]; and the National Natural Science Foundation of China [Project: 81473037].