Combined antihypertensive drugs have become the basic method of treating hypertension. Olmesartan and amlodipine, as representative drugs of angiotensin receptor blockers and calcium channel blockers, were developed as a compound formulation for antihypertensive treatment. The purpose of this study was to evaluate the bioequivalence of olmesartan medoxomil/amlodipine besylate tablet (20 mg/5 mg) under fasting and fed conditions in healthy Chinese volunteers. A phase 1 randomized, open-label, 2-period, single-dose crossover study (n = 56) was designed, with subjects under fasting (n = 28) or fed (n = 28) conditions. Of the 56 enrolled participants, 55 healthy volunteers completed the study. Blood samples for pharmacokinetic analysis were collected from 1.5 hours before dosing to 168 hours after dosing. The 90%CIs for the geometric mean ratios of maximum plasma drug concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration and AUC from time 0 to infinity of the test/reference were all within the acceptance range for bioequivalence (80%-125%). The data showed that the absorption of amlodipine is not affected by food, but the exposure of olmesartan (both AUC from time 0 to the last measurable concentration and AUC from time 0 to infinity were P < .05) reduced significantly after consuming a high-fat meal, which indicates that the effects of food on olmesartan exposure in healthy Chinese were clinically relevant. During the study, there were no suspected serious adverse reactions or serious adverse events. All adverse events were determined to be mild after Common Terminology Criteria for Adverse Events 5.0 evaluation. These results indicated that both the test and reference formulations were bioequivalent with similar safety profiles.
Keywords: amlodipine; bioequivalent; fasting and fed; fixed-dose combination; olmesartan.
© 2022, The American College of Clinical Pharmacology.