Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension

Abstract

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean + standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 142 ng/ml, 2.4 + 1.1 h, and 3,109 + 1,033 ng. h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 31, 64 24, 41 + 17, and 29 + 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.

Pharmacokinetics of azithromycin in pediatric patients with acute otitis media

“…Interestingly, the C max and AUC 0-24 values in these patients were lower than the C max of 383 ng/ml and the AUC 0-24 of 3,109 ng ⅐ h/ml reported for 6-to 15-year-old patients with streptococcal pharyngitis after the administration of similar dosages (11). However, mean concentrations in serum for the two studies show similar rates of decline following peak concentrations, suggesting that the distribution and elimination rates for the two populations were similar.…”

“…The pharmacokinetics of azithromycin have been studied in children 6 to 15 years of age with the diagnosis of streptococcal pharyngitis. In these patients, a once-daily administration led to sustained systemic exposure to the drug (11). Little is known, however, about the pharmacokinetics of azithromycin in children between the ages of 7 months and 5 years.…”

Safety and effectiveness of azithromycin in the treatment of respiratory infections in children

“…In the last 20 years, resistance to bacteria causing respiratory tract infections has increased, especially strains of S. pneumoniae, but reports on how this affects the results of the treatment are scarce and controversial [17][18][19][20] . Azithromycin also achieves prolonged and higher tissue concentrations and has a potential immunomodulatory effect 21,22 .…”

Ensuring Safe and Effective Medication Use in Pediatric Patients

“…We did pivotal studies to characterize its pharmacokinetics, documenting adequate concentrations in children with respiratory tract infections. 13 These studies, combined with our efficacy and safety studies, were submitted to the US Food and Drug Administration (FDA) for its approval in children.…”