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Pharmacokinetic study of piperacillin in newborns relating to gestational and postnatal age
N Kacet1, M Roussel-Delvallez, C Gremillet
1Neonatal Unit, Hôpital Calmette, Centre Hospitalier Universitaire, Lille, France.
Insights
Piperacillin dosing in neonates requires adjustment based on gestational age. Premature infants need more frequent dosing to maintain therapeutic piperacillin serum concentrations.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Neonatal populations exhibit significant pharmacokinetic variability.
- Understanding piperacillin disposition is crucial for optimizing neonatal therapy.
- Gestational age influences drug metabolism and elimination in newborns.
Purpose of the Study:
- To characterize piperacillin pharmacokinetics in neonates.
- To evaluate the impact of gestational age on piperacillin elimination half-life and clearance.
- To establish evidence-based dosing recommendations for piperacillin in neonates.
Main Methods:
- Pharmacokinetic analysis of piperacillin in 28 neonates (29-42 weeks gestational age).
- Intravenous piperacillin injections (75 mg/kg) administered during the first and second weeks of life.
- Serum piperacillin concentrations measured using high-pressure liquid chromatography (HPLC).
- One-compartment open model used to describe drug disposition.
Main Results:
- Piperacillin elimination half-life and total body clearance were significantly influenced by gestational age.
- Infants with lower gestational ages (29-35 weeks) exhibited longer half-lives and lower clearance rates compared to those closer to term (38-42 weeks).
- Volume of distribution remained consistent across all gestational age groups.
Conclusions:
- Piperacillin dosing regimens must be tailored to gestational age for optimal therapeutic outcomes.
- Neonates <36 weeks gestational age require adjusted dosing frequencies (e.g., every 12 hours initially, then every 8 hours).
- Full-term newborns may receive standard 75 mg/kg doses but require increased frequency (3-4 times daily) over time.
Abstract:
The pharmacokinetics of piperacillin after a single 75-mg/kg intravenous injection as analyzed in 28 neonates with gestational ages of 29 to 40 weeks (A = 29 to 31 weeks, B = 33 to 35 weeks, C = 38 to 42 weeks) and birth weights of 860 to 3900 g during 35 courses. Serum concentrations of piperacillin were determined by high pressure liquid chromatography. A one compartment open model characterized the disposition of piperacillin. Twenty courses were given between Day 3 and Day 5 of life. The elimination half-life and total body clearance were related to gestational age. Differences were significant between Groups A and B and Group C for half-life (4.3 +/- 1.9 and 3.35 +/- 0.75 vs. 2.47 +/- 0.72 hours) and for clearance (1.68 +/- 0.6 and 1.8 +/- 0.4 vs. 2.46 +/- 0.36 ml/min/kg). Volumes of distribution were similar in the 3 groups, from 516 +/- 108 to 633 +/- 226 ml/kg. Fourteen courses were given from Day 9 to Day 11 of life. The same differences were observed between Groups A and B and Group C. Elimination half-life was significantly reduced with simultaneous increase of the total body clearance. In clinical practice, 75-mg/kg intravenous injections every 12 hours during the first week of life and every 8 hours in the second week provide appropriate concentrations in infants of less than 36 weeks gestational age. In full term newborns the 75-mg dosage is appropriate but the number of injections must be increased to 3/24 h for the first week and 4 times daily thereafter.