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The pharmacokinetics of ticarcillin/clavulanate acid in neonates
Insights
This study investigated the pharmacokinetics of ticarcillin and clavulanate in neonates. Dosing achieved adequate drug concentrations in both preterm and full-term infants, with some variations in low birth weight preterm infants.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Neonates, particularly preterm infants, exhibit unique pharmacokinetic profiles due to immature organ systems.
- Ticarcillin and clavulanate combination is frequently used for bacterial infections in neonates.
- Understanding drug disposition in this population is crucial for optimizing therapeutic outcomes and minimizing toxicity.
Purpose of the Study:
- To evaluate the pharmacokinetics of a 25:1 combination of ticarcillin and clavulanate in preterm and full-term neonates.
- To determine if standard dosing regimens achieve adequate therapeutic drug concentrations in different neonatal subgroups.
- To identify any potential drug accumulation or altered pharmacokinetic parameters in specific neonatal populations.
Main Methods:
- A pharmacokinetic study involving nine preterm and seven full-term neonates.
- Administration of specific doses of ticarcillin and clavulanate via slow infusion.
- Serial blood sampling to determine drug concentrations (Cmax, T, AUC, Vd) at various time points.
- Patient stratification into three groups based on gestational age and birth weight.
Main Results:
- Full-term neonates (Group 1) and higher birth weight preterm neonates (Group 2) showed comparable pharmacokinetic parameters for both ticarcillin and clavulanate.
- Drug accumulation was not observed in Groups 1 and 2.
- Two low birth weight preterm neonates (Group 3) exhibited distinct pharmacokinetic profiles, including delayed peak concentrations in one and drug accumulation in the other, without apparent toxicity.
Conclusions:
- The studied doses of ticarcillin and clavulanate achieve adequate peak and trough serum concentrations in both preterm and full-term neonates.
- Neonates, especially those with very low birth weight, may exhibit altered drug disposition requiring careful monitoring.
- Further investigation into the pharmacokinetics of this combination in specific low birth weight preterm populations is warranted.
Abstract:
The pharmacokinetics of a 25:1 combination of ticarcillin and clavulanate were studied in nine pre-term and seven full-term neonates. Pre-term neonates with a gestational age ranging from 30 to 36 weeks received 83.3 mg of ticarcillin and 3.3 mg of clavulanate per kg bw and full-term neonates with a gestational age from 39 to 43 weeks received 100 mg of ticarcillin and 4 mg of clavulanate per kg bw 8-hourly, each by a slow infusion over 10 min. Serum was sampled 15, 30, 60, 120, 240 and 480 min after the first dose and trough samples were additionally obtained on the fourth day of treatment. The patients were allocated to Groups 1-3 on the basis of the pharmacokinetic characteristics obtained. Group 1 comprised seven full-term babies. Group 2 contained seven pre-term neonates with a birth weight between 1915 and 2650 g and Group 3 consisted of two pre-term neonates of low birth weight (1400 g and 1640 g). Mean (+/- S.E.) pharmacokinetic characteristics of Group 1 patients for ticarcillin were: Cmax = 404.9 mg/l (36.0); T = 2.68 h (0.23); AUC = 1287 h.mg/l (69); Vd = 266 ml/kg (28) and for clavulanate: Cmax = 15.0 mg/l (1.2); T = 1.39 h (0.12); AUC = 30.1 h.mg/l (1.7); Vd = 263 ml/kg (22). Corresponding parameters for Group 2 patients for ticarcillin were: Cmax 278.7 mg/l (30.4); T = 4.20 h (0.49); AUC = 1107 h.mg/l (57); Vd = 338 ml/kg (35) and for clavulanate: Cmax = 8.4 mg/l (0.56); T = 2.56 h (0.18); AUC = 27.1 h.mg/l (2.0); Vd = 414 ml/kg (29). Drug accumulation was not observed in patients of Groups 1 and 2. Each of the two patients of Group 3 presented a pharmacokinetic profile which was considerably different from those observed in Groups 1 and 2. While in patients of the latter group the peak serum concentrations were achieved at 15-30 min after the end of infusion, these concentrations occurred between 120 and 240 min in one of the Group 3 patients. In the other Group 3 patient a remarkable drug accumulation was noted but was not associated with clinical or laboratory evidence of toxicity. These data show that ticarcillin and clavulanic acid in these dose ranges achieved adequate peak and trough concentrations in pre-term and full-term neonates.