PHARMACOKINETIC-BASED TICARCILLIN CLAVULANIC ACID DOSE RECOMMENDATIONS FOR INFANTS AND CHILDREN/

The pharmacokinetic characteristics of ticarcillin and clavulanic acid were determined after the first dose (n = 22) and again under steady- state conditions (n = 16) in a group of infants and children. Study su bjects ranged in age from 1 month to 9.3 years; all but 3 study patien ts were 6 months of age or older. Each patient received 50 mg of ticar cillin and 1.7 mg of clavulanic acid (30:1 ratio) per kg of body weigh t given intravenously every 4 hours. Elimination half-life, steady-sta te volume of distribution, and body clearance averaged 1.1 hours, 0.22 L/kg, and 2.7 ml/min/kg, respectively, for ticarcillin, and 0.9 hours , 0.4 L/kg, and 6.2 ml/min/kg, respectively, for clavulanic acid. A to tal of 71% of the ticarcillin and 50% of the clavulanic acid dose were excreted unchanged in the urine over the 4-hour sampling period. Corr esponding renal clearances averaged 2.1 and 3.2 ml/min/kg for ticarcil lin and clavulanic acid, respectively. No differences were observed be tween first dose and steady-state evaluations in the pharmacokinetic b ehavior of either agent. In contrast, the pharmacokinetic behavior of clavulanic acid was significantly different from that observed for tic arcillin. These pharmacokinetic data combined with known in vitro susc eptibilities of important clinical pathogens support a dose of 80 mg o f ticarcillin and 2.7 mg/kg clavulanic acid per kg body weight given a s a fixed dose combination every 8 hours for the treatment of most sys temic infections that occur outside the central nervous system.