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Published on: August 30, 2018
Evaluation of ceftriaxone pharmacokinetics in hospitalized Egyptian pediatric patients
Mohamed W Eldougdoug1, Doaa M Youssef2, Amal S El-Shal3,4
1Department of Pharmacy Practice, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. mohammed0494@gmail.com.
Insights
This study on critically ill children found ceftriaxone pharmacokinetics vary with kidney function. Monitoring liver enzymes and bilirubin is recommended during treatment to prevent potential adverse effects.
Area of Science:
- Pharmacology
- Pediatrics
- Clinical Pharmacy
Background:
- Ceftriaxone is a key antibiotic for pediatric infections.
- Understanding its pharmacokinetics in critically ill children is crucial for effective treatment.
- Previous studies have shown varied pharmacokinetic models for ceftriaxone.
Purpose of the Study:
- To evaluate ceftriaxone pharmacokinetics in critically ill Egyptian children.
- To assess the impact of renal function on ceftriaxone clearance and distribution.
- To monitor for adverse drug effects, specifically liver function and bilirubin levels.
Main Methods:
- Pharmacokinetic analysis of ceftriaxone in 24 hospitalized pediatric patients (2.5 months–12 years).
- Blood samples analyzed for total and free ceftriaxone concentrations using HPLC.
- Data fitted to a one-compartment model using Phoenix Winnonlin software.
Main Results:
- Ceftriaxone clearance correlated with renal function (eGFR).
- Reduced kidney function decreased clearance, while augmented clearance increased it.
- Increased volume of distribution and free fraction were observed, especially with hypoalbuminemia.
- Mild increases in total bilirubin and liver enzymes (ALT, AST) were noted.
Conclusions:
- The standard ceftriaxone regimen (50-100 mg/kg) generally provides adequate coverage for critically ill children.
- Ceftriaxone clearance is significantly influenced by individual renal function.
- Monitoring total bilirubin and liver enzymes is essential during ceftriaxone therapy, particularly for prolonged durations or in patients with pre-existing high values, due to potential cholestasis risks.
Abstract:
This study aimed to evaluate ceftriaxone pharmacokinetics that affects the achievement of targets in the treatment of critically ill children (meningitis, pneumonia, urinary tract infection, peritonitis, and infective endocarditis( who were admitted to Zagazig University Pediatric hospital in Egypt to monitor for the drug adverse effects.Blood samples were obtained from 24 hospitalized pediatric patients (ages ranging from 2.5 months to 12 years) after administering the calculated dose of ceftriaxone via intravenous bolus route. Then, ceftriaxone plasma concentrations were measured using a validated HPLC method with ultraviolet detection. The pharmacokinetic analysis was conducted using Phoenix Winnonlin Program® software.Data for total and free ceftriaxone best fitted on a one-compartment model with the first-order elimination process. Clearance of ceftriaxone is reduced for patients with reduced kidney function and increased with those with augmented renal clearance. The volume of distribution and the free fraction are increased in these patients, especially those with hypoalbuminemia with a shorter half-life time were detected. A slight increase in total bilirubin and liver enzymes has been observed after treatment with ceftriaxone in these patients. Conclusion: In most critically ill pediatric patients, the current ceftriaxone treatment regimen (50 to 100 mg/kg) offers adequate pathogenic coverage. The clearance of free ceftriaxone in all patients correlates well with their renal function (eGFR), with r2 = 0.7252. During therapy with ceftriaxone at all doses ranging from 50 to 100 mg/kg, a rise in total bilirubin was observed in these patients. Moreover, liver enzymes (ALT and AST) increased moderately (p 0.0001). So, it is recommended to monitor total bilirubin and liver enzymes during the treatment with ceftriaxone, especially for a long duration (more than 5 days) or use another agent in patients with high baseline values. What is Known: • The dosing regimen of ceftriaxone (50 to 100 mg/kg) provided optimum therapeutic outcomes. • Some studies show data for total and free Ceftriaxone best fitted on a one-compartment model while other studies show data for total and free Ceftriaxone best fitted on a two-compartment model. What is New: • Up to my knowledge this is the first study ,considering individual pharmacokinetic analysis, conducted on hospitalized Egyptian pediatric population most of them with reduced kidney function with ages ranging from 2.5 months to 12 years. Data for total and free Ceftriaxone best fitted on a one-compartment model with linear clearance of the free ceftriaxone. • In all patients, total bilirubin and liver function tests were mildly increased, making them at risk for cholestasis or ceftriaxone-induced cholestatic hepatitis.
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