The pharmacokinetics of ticarcillin, clavulanic acid and their combination

The pharmacokinetics of ticarcillin and clavulanic acid were examined both alone and combined (3.0 and 5.0 g ticarcillin + 0.2 g clavulanic acid as 3.2 or 5.2 g Timentin) after a 15-min infusion in ten healthy volunteers. The serum kinetics of both ticarcillin and clavulanic acid were described by an open two-compartment model. After the end of the infusion, the serum concentrations of ticarcillin (clavulanic acid) ranged between 576.2 +/- 98.7 mg/l (26.1 +/- 2.6 mg/l) after separate and 621.8 +/- 62.6 mg/l (22.9 +/- 4.6 mg/l) after combined administration. Both substances showed similar kinetic behaviour in serum with a T1/2 beta of 74.8 +/- 11.5 min for ticarcillin and 76.6 +/- 4.6 min for clavulanic acid. The total clearance of clavulanic acid was 158 +/- 23 ml/min and thus clearly exceeded that of ticarcillin (112 +/- 9 ml/min). The recovery rate in the 24 h urine was 41.3% for clavulanic acid as compared to 79.4% for ticarcillin. Concomitant administration of both substances had little effect on the kinetics of either agent alone. With increasing doses of ticarcillin, a decrease of the non-renal clearance of clavulanic acid was observed. The ratio of the two compounds in serum varied from 25:1 (for 5.2 g Timentin, 15:1 for 3.2 g Timentin) at the time of administration to 59:1 (34:1, respectively) 4 h after infusion.