Pharmacokinetics of azithromycin after single- and multiple-doses in children.
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.


METHODS
Open-label, nonrandomized pharmacokinetic study.


METHODS
Two pediatric hospitals.


METHODS
Twelve children with cancer admitted to the inpatient unit for empiric antibiotic treatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy


METHODS
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.


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.


CONCLUSIONS
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.
Stevens
R C
RC
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, University of Tennessee, Memphis 38015-2794, USA.
Reed
M D
MD
Shenep
J L
JL
Baker
D K
DK
Foulds
G
G
Luke
D R
DR
Blumer
J L
JL
Rodman
J H
JH
D000293:Adolescent; D000375:Aging / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism
D000900:Anti-Bacterial Agents; D017963:Azithromycin