Pharmacokinetics of Amoxicillin and Clavulanate Potassium for Suspension (200 mg/28.5 mg) in Healthy Subjects: Sample Add Stabilizer Study and Food Effects

Abstract The present study compares the pharmacokinetics of amoxicillin and clavulanate potassium suspension (200 mg/28.5 mg) during fasting and postprandial conditions, and the sample adds a stabilizer study. Two randomized, crossover trials were conducted in an open‐label, single‐center study (a fasting trial and a postprandial trial). In each part of the study, the subjects were randomly assigned to receive either test or reference products (200 mg/28.5 mg) in a 1:1:1 ratio, followed by the alternative products after a 7‐day washout period. Plasma amoxicillin and clavulanic acid concentrations were analyzed by liquid chromatography–tandem mass spectrometry. WinNonlin software was used to evaluate the pharmacokinetic parameters (noncompartmental model). The formulations were considered bioequivalent if the geometric means of area under the plasma concentration–time curve (AUC) and maximum plasma concentration (C max ) of amoxicillin and clavulanic acid were within the predetermined bioequivalence range established by average bioequivalence (ABE) or reference‐scaled ABE. Tolerability was assessed throughout the study. The postprandial trial and the fasting study each had 12 volunteers. Under fasting and postprandial conditions, the 90%CI for the ratio of geometric means of amoxicillin of C max , AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the ABE acceptance limits (80%‐125%); the geometric means of clavulanic acid of C max (critbound, –0.03; point estimate, 1.07) were within the reference‐scaled ABE acceptance limits, and the AUC from time 0 to the last measurable concentration and AUC from time 0 to infinity were within the ABE acceptance limits (80%–125%). Time to maximum concentration of amoxicillin was delayed 1.0 hour with high‐fat meals compared to fasting conditions. Meantime, high‐fat meals decreased the exposure of clavulanic acid by nearly 40%. No serious adverse events were found among the subjects. The bioequivalence of test and reference amoxicillin and clavulanate potassium for suspension was validated in this study under fasting and postprandial conditions.