The disposition of clavulanic acid in man.

Following oral administration of potassium 14C-clavulanate to four human subjects, at least 73% of the radioactive dose was absorbed. The mean absolute bioavailability was 64%. Absorption was rapid with peak plasma concentrations of radioactivity and clavulanic acid (2-6 micrograms/ml) occurring between 45 min and three hours after dosing. Values for the volume of distribution at steady-state and terminal half-life of clavulanic acid in the plasma were 12.01 and 0.8 h respectively. Following intravenous administration of clavulanic acid to the same subjects, the clearance, and volume of distribution at steady-state were 0.21 l/min, and 12.01, respectively. Clavulanic acid was the major radioactive component present in 0-24 h urine following oral dosing (23% of the dose). The two major metabolites were 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid (15% of the dose) and 1-amino-4-hydroxybutan-2-one (8.8% of the dose). Clavulanic acid and 1-amino-4-hydroxybutan-2-one were the major components in plasma following oral administration (52 and 21% of plasma radioactivity respectively at two hours after dosing). The major route of excretion of radioactivity following oral administration was via the urine (73% of the dose). Most of this radioactivity was excreted in the first 24 h after dosing (68% of the dose). The renal clearance of clavulanic acid was 0.1 l/min. Elimination of radioactivity also occurred via the expired air (17% of the dose) and the faeces (8% of the dose).