Pharmacokinetics of Amoxicillin/Clavulanic Acid Combination after Oral Administration of New Suspension Formulations in Human Volunteers

The pharmacokinetic properties of amoxicillin and clavulanic acid when used aloneor in combination may be different and show interaction between these two agentsthat might decrease the absolute bioavailability of clavulanic acid. in an open,randomized, replicated latin square under fasting condition, pharmacokinetics ofnew formulations of amoxicillin/clavulanic acid were compared with a referenceformulation after single dose administration in 15 healthy male volunteers. subjectswere given equal molar doses of new suspension formulations ofamoxicillin/clavulanic acid (312 mg/5 ml or 156 mg/5 ml) or augmentin® (312 mg/5ml) as the reference product. the wash-out period was one week between theadministrations of these antibacterial agents. blood samples were collected exactlybefore and after drug administration of each of the formulations at different timepoints up to 6 h. the concentrations of the antibiotics in plasma were measured byvalidated hplc methods. three formulations exhibited a similar mean cmax of about7.5±1.6 mg/l after tmax of about 75±25 min. for amoxicillin and cmax of about 2.5±0.6mg/l after tmax of about 61±15 min. for clavulanic acid. the auc0-inf (total areaunder the curve) for amoxicillin was about 1278±172 g.min/ml and it was about354±66 g.min/ml for clavulanic acid. there were no significant differences inpharmacokinetic parameters among these formulations. pharmacokinetic parametersof amoxicillin and clavulanic acid found in this study were similar to previouslypublished data. the two generic formulations investigated in this study proved tobe bioequivalent with brand-name augmentin® with regard to the pharmacokineticparameters cmax, auc0-t, auc0-inf and tmax. moreover, the parametric confidenceintervals (90%) for the ratio of the cmax, tmax, auc0-t, and auc0-q values liebetween 0.8-1.2 based on log transformed values. we may conclude that the twonew formulations are bioequivalent with the reference suspension and could beconsidered equally effective in medicinal practice. moreover, there were nointeraction in pharmacokinetic parameters between amoxicillin and clavulanicacid. no serious adverse event was observed with the studied drugs.