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 subjects ranged in age from 1 month to 9.3 years; all but 3 study patients were 6 months of age or older. Each patient received 50 mg of ticarcillin and 1.7 mg of clavulanic acid (30:1 ratio) per kg of body weight given intravenously every 4 hours. Elimination half-life, steady-state 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 total of 71% of the ticarcillin and 50% of the clavulanic acid dose were excreted unchanged in the urine over the 4-hour sampling period. Corresponding renal clearances averaged 2.1 and 3.2 mL/min/kg for ticarcillin and clavulanic acid, respectively. No differences were observed between first dose and steady-state evaluations in the pharmacokinetic behavior of either agent. In contrast, the pharmacokinetic behavior of clavulanic acid was significantly different from that observed for ticarcillin. These pharmacokinetic data combined with known in vitro susceptibilities of important clinical pathogens support a dose of 80 mg of ticarcillin and 2.7 mg/kg clavulanic acid per kg body weight given as a fixed dose combination every 8 hours for the treatment of most systemic infections that occur outside the central nervous system.
Reed
M D
MD
Division of Pediatric Pharmacology, Rainbow Babies and Childrens Hospital, Cleveland, OH 44106-5000, USA.
Yamashita
T S
TS
Blumer
J L
JL
D002648:Child; D002675:Child, Preschool; D002969:Clavulanic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D013982:Ticarcillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D065093:beta-Lactamase Inhibitors
D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin