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Pharmacokinetic-based ticarcillin/clavulanic acid dose recommendations for infants and children
M D Reed1, T S Yamashita, J L Blumer
1Division of Pediatric Pharmacology, Rainbow Babies and Childrens Hospital, Cleveland, OH 44106-5000, USA.
Insights
This study determined the pharmacokinetics of ticarcillin and clavulanic acid in children, finding no significant differences between first dose and steady-state. The data support an every-8-hour dosing regimen for infections.
Area of Science:
- Pharmacology
- Pediatric Therapeutics
- Antibiotic Pharmacokinetics
Background:
- Understanding the pharmacokinetics of antibiotics in pediatric populations is crucial for optimizing treatment efficacy and safety.
- Ticarcillin and clavulanic acid are commonly used antibiotics, but their pharmacokinetic profiles in infants and children require specific investigation.
Purpose of the Study:
- To characterize the pharmacokinetic properties of ticarcillin and clavulanic acid in pediatric patients.
- To evaluate potential differences in pharmacokinetics between initial and steady-state dosing.
- To inform optimal dosing recommendations for ticarcillin-clavulanic acid in children.
Main Methods:
- Prospective pharmacokinetic study involving 22 infants and children (1 month to 9.3 years).
- Intravenous administration of ticarcillin (50 mg/kg) and clavulanic acid (1.7 mg/kg) every 4 hours.
- Analysis of drug concentrations in plasma and urine to determine pharmacokinetic parameters like half-life, volume of distribution, and clearance.
Main Results:
- Average elimination half-lives were 1.1 hours for ticarcillin and 0.9 hours for clavulanic acid.
- Body clearances were 2.7 mL/min/kg for ticarcillin and 6.2 mL/min/kg for clavulanic acid.
- No significant differences in pharmacokinetic behavior were observed between first-dose and steady-state conditions for either drug.
Conclusions:
- The pharmacokinetic profiles of ticarcillin and clavulanic acid differ significantly in pediatric patients.
- The findings support a revised dosing regimen of 80 mg/kg ticarcillin and 2.7 mg/kg clavulanic acid every 8 hours for systemic infections.
- This optimized dosing may improve therapeutic outcomes in pediatric patients treated with this antibiotic combination.
Abstract:
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.