PHARMACOKINETICS OF AZITHROMYCIN AFTER SINGLE-DOSE AND MULTIPLE-DOSESIN CHILDREN

Study Objective. To characterize the disposition and tolerance of azit hromycin after single and multiple oral doses of 12 mg/kg in children with and without cancer. Design. Open-label, nonrandomized pharmacokin etic study. Setting. Two pediatric hospitals. Patients. Twelve childre n with cancer admitted to the inpatient unit for empiric antibiotic tr eatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy. Interventions. Patients received azithromycin sus pension either as a single dose or daily dose every morning for 5 cons ecutive days. Serial blood samples were collected up to 120 hours afte r 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 o f insufficient concentration-time data. The mean +/- SD estimates of o ral clearance, terminal half-life, maximum concentration in serum (C-m ax), and time to achieve C-max in the 23 evaluable patients were 4.83 +/- 3.59 L/hour/kg, 54.5 +/- 36.4 hours, 318.2 +/- 174.5 mu g/L, and 2 .4 +/- 1.1 hours, respectively. These estimates did not differ between single-dose (14 patients) and multiple-dose (9 patients) groups. Phar macokinetic parameters were not different between the 11 children with cancer and the 12 without cancer. Conclusion. Azithromycin 12 mg/kg r esults in proportionately higher serum concentrations than previously published results for lower doses (5 mg/kg). Variability in concentrat ion profiles among patients is substantial, and age or other yet unide ntified clinical factors may explain some of the differences observed.