Pharmacokinetic studies of the urinary excretion of clavulanic acid in man.

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Abstract
A pharmacokinetic investigation on the urinary excretion of clavulanic acid in man was carried out. Combinations of clavulanic acid (125 mg) and amoxicillin (250 mg) were given orally to human subjects, and the subsequent urinary concentrations of intact clavulanic acid, amoxicillin and the latter''s metabolites (penicilloic acid and penamaldic acid) were determined by the high performance liquid chromatography method. From the urinary excretion rate vs. time curves for each species, the values of cumulative excretion amount at infinite time and of mean residence time were estimated by means of the moment analysis method. When clavulanic acid was dosed in combination with amoxicillin, 27-45% of the dosed amount of clavulanic acid was excreted in the urine as an intact form with a mean residence time of 1.6-2.1 h after administration, while the corresponding values for amoxicillin were 56-73% (including metabolites) and 2.0-2.6 h (for the intact form). Clavulanic acid may undergo less absorption (and/or more extensive metabolism and extra-urinary excretion) and faster urinary excretion than amoxicillin. By comparison of the results with those obtained after individual doses of clavulanic acid and amoxicillin to the same subjects, it was found that there was no appreciable kinetic interaction between clavulanic acid and amoxicillin ascribable to the combined dose, although the analysis of variance indicated that the difference in the excreted amounts of penamaldic acid of amoxicillin between combined and individual doses was significant at the 5% level.