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Pharmacokinetics of azithromycin after single- and multiple-doses in children
R C Stevens1, M D Reed, J L Shenep
1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, University of Tennessee, Memphis 38015-2794, USA.
Insights
Azithromycin at 12 mg/kg in children is well tolerated and achieves higher serum concentrations than lower doses. Pharmacokinetic parameters were similar between single and multiple doses, and between children with and without cancer.
Area of Science:
- Pediatric Pharmacology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Azithromycin is a widely used antibiotic in pediatric populations.
- Understanding its pharmacokinetic profile in children, especially those with cancer, is crucial for optimizing treatment.
- Previous studies have evaluated lower doses, necessitating further investigation into higher doses.
Purpose of the Study:
- To determine the pharmacokinetic disposition and tolerance of azithromycin in children receiving a 12 mg/kg oral dose.
- To compare azithromycin pharmacokinetics after single versus multiple (5-day) doses.
- To assess differences in azithromycin disposition between pediatric patients with and without cancer.
Main Methods:
- An open-label, nonrandomized pharmacokinetic study was conducted in two pediatric hospitals.
- Twenty-eight pediatric patients (12 with cancer, 16 without) received azithromycin suspension (12 mg/kg) as a single or 5-day course.
- Serial blood samples were collected to determine pharmacokinetic parameters using a two-compartment absorption model.
Main Results:
- Azithromycin was generally well tolerated in all 28 patients; one patient with cancer experienced abdominal cramps.
- Pharmacokinetic parameters (oral clearance, half-life, Cmax, Tmax) were estimated in 23 patients.
- No significant differences in pharmacokinetic parameters were observed between single-dose and multiple-dose regimens, or between children with and without cancer.
Conclusions:
- A 12 mg/kg oral dose of azithromycin leads to proportionally higher serum concentrations compared to lower doses (5 mg/kg).
- Substantial inter-patient variability in azithromycin concentration profiles was noted.
- Age and other unidentified clinical factors may contribute to the observed variability in azithromycin disposition.
Study Objective:
To characterize the disposition and tolerance of azithromycin after single and multiple oral doses of 12 mg/kg in children with and without cancer.
Design:
Open-label, nonrandomized pharmacokinetic study.
Setting:
Two pediatric hospitals.
Patients:
Twelve children with cancer admitted to the inpatient unit for empiric antibiotic treatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy
Interventions:
Patients received azithromycin suspension either as a single dose or daily dose every morning for 5 consecutive days. Serial blood samples were collected up to 120 hours after a single dose or during and after multiple doses to characterize the pharmacokinetic parameters estimated for a two-compartment absorption model.
Measurements And Main Results:
All 28 patients were evaluable for safety. Azithromycin was well tolerated except in one patient with cancer who experienced abdominal cramps and withdrew from the study. Pharmacokinetic results were not determined in five patients because of insufficient concentration-time data. The mean +/- SD estimates of oral clearance, terminal half-life, maximum concentration in serum (Cmax), and time to achieve Cmax in the 23 evaluable patients were 4.83 +/- 3.59 L/hour/kg, 54.5 +/- 36.4 hours, 318.2 +/- 174.5 microg/L, and 2.4 +/- 1.1 hours, respectively. These estimates did not differ between single-dose (14 patients) and multiple-dose (9 patients) groups. Pharmacokinetic parameters were not different between the 11 children with cancer and the 12 without cancer.
Conclusion:
Azithromycin 12 mg/kg results in proportionately higher serum concentrations than previously published results for lower doses (5 mg/kg). Variability in concentration profiles among patients is substantial, and age or other yet unidentified clinical factors may explain some of the differences observed.