Background: The pharmacokinetics of bisoprolol and amlodipine administered as a fixed-dose combination (FDC) tablet have not been sufficiently studied in healthy Chinese subjects to support a medical need for using the FDC in hypertension.
Objective: This study was conducted to compare the pharmacokinetic profiles of the bisoprolol-amlodipine FDC tablet with the bisoprolol tablet and amlodipine tablet administered concomitantly under both fasting and fed conditions.
Methods: An open-label, randomized, two-period, two-sequence crossover study was designed under both fasting and fed conditions. The plasma concentrations of bisoprolol and amlodipine were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence.
Results: The point estimate of geometric mean ratios of Cmax and AUC from the time of dosing to the last measurable concentration (AUCt) for bisoprolol were 97.85% and 99.46% in the fasting state, and 93.87% and 98.95% in the fed state, respectively. For amlodipine, the geometric mean ratios of Cmax and AUCt were 100.03% and 96.76% in the fasting state, and 106.56% and 103.07% in the fed state. No cases of treatment-emergent adverse events were reported during the entire study period.
Conclusions: Bioequivalence was achieved for bisoprolol and amlodipine FDC under both fasting and fed conditions, and all treatments were safe and well tolerated by all study subjects.
Trial registration: ClinicalTrials.gov: NCT03226275.