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[Mezlocillin concentrations in the serum of children with impaired renal function]
Abstract:
Mezlocillin was administered as an intravenous bolus injection to eight children, aged 4-15, requiring antibiotic therapy; the dose was either 75 mg/kg or 37.5 mg/kg. All of the patients had advanced renal insufficiency. Five of the children required chronic intermittent hemodialysis. The microbiological method of Grove and Randall was used for the quantitative determination of mezlocillin in the serum. Ten minutes after the injection, the concentration of mezlocillin in the serum was approximately 90 mg/l and 40 mg/l, respectively. The determinations 30 and 60 minutes after the injection showed that the mezlocillin concentrations had fallen rapidly to approximately 30 mg/l and 20 mg/l, respectively. The mezlocillin concentrations were still approximately 2 mg/l and 1 mg/l, respectively, 12 hours after administration. For the period between 10 and 60 minutes, the half-lives were between 33 and 57 minutes. In general, we can conclude that a single bolus injection of 75 mg/kg will result in mezlocillin concentrations in the serum of uremic children which allow us to expect good antibacterial efficacy, at least for the first few hours following the injection. On the basis of our studies, half the dosage does not appear to be sufficient.
Insights
A 75 mg/kg dose of mezlocillin in children with advanced renal insufficiency achieved effective serum concentrations for several hours. Lower doses were insufficient, indicating the higher dose is necessary for adequate antibacterial efficacy in uremic pediatric patients.
Area of Science:
- Pharmacology
- Pediatric Nephrology
Context:
- Antibiotic therapy in pediatric patients with renal insufficiency is challenging.
- Uremic conditions significantly alter drug pharmacokinetics.
- Mezlocillin is a penicillin antibiotic used for bacterial infections.
Purpose:
- To determine the pharmacokinetic profile of mezlocillin in children with advanced renal insufficiency.
- To evaluate the efficacy of different mezlocillin dosages (75 mg/kg vs. 37.5 mg/kg) in this patient population.
Summary:
- Eight children (aged 4-15) with advanced renal insufficiency received intravenous bolus injections of mezlocillin (75 mg/kg or 37.5 mg/kg).
- Serum mezlocillin concentrations were measured using a microbiological assay.
- Peak concentrations at 10 minutes were ~90 mg/l (75 mg/kg) and ~40 mg/l (37.5 mg/kg), rapidly declining thereafter.
- Serum half-lives between 10-60 minutes ranged from 33-57 minutes.
- The 75 mg/kg dose resulted in concentrations expected to provide good antibacterial efficacy for several hours, while the 37.5 mg/kg dose was insufficient.
Impact:
- The 75 mg/kg dose of mezlocillin appears to be effective for initial treatment in pediatric patients with renal insufficiency.
- This study provides crucial dosing information for optimizing mezlocillin therapy in uremic children.
- Findings support the need for higher antibiotic doses in patients with impaired renal function to achieve therapeutic levels.