PHARMACOKINETIC AND CLINICAL STUDIES WITH AZITHROMYCIN (CAPSULE) IN THE PEDIATRIC FIELD

Pediatric Study Group of azithromycin

Abstract

Azithromycin (AZM) in 100 mg capsules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.9% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition, AZM concentrations were determined in blood samples from 9 patients and in urine samples from 12 patients to examine pharmacokinetic characteristics of AZM.
1. Absorption and excretion: C. was 0.45±0.28μg/ml, T 1/2 was 52.7±20.2 hours, and AUC0-∞ was 12.09±4.93μghr/ml in the 9 patients each of whom received 8.5 to 14.3 mg/kg AZM. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 8.5 to 14.7 mg/kg AZM in 12 patients and the average urinary recovery rate in 120 hours was 7.3±2.8%.
2. Clinical efficacy: The study received 139 entries and 119 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate, combining both “Excellent” and “Good” cases, was 100% for 40 cases in which pathogens were identified, classified as Group A. The efficacy rate was 97.5% for the remaining 79 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 98.3%. For the 31 cases where the patients had failed to respond to the previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 93.5%.
3. Adverse reactions and abnormal laboratory tests: 8 incidents of diarrhea, skin rashes, urticaria, or vomiting were found in 7 patients (5.4%) of 130 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 7 patients including 2 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 10 patients (9.3%), an increase in eosinophils in 12 (11.4%), an increase in platelet count in 1 (1.0%), an elevation of GOT in 3 (3.1%), an elevation of GPT in 6 (6.2%), and an elevation of LDH in 1 (1.1%). The abnormalities were transient and did not require particular intervention. Moreover, none of the patients indicated clinical signs associated with the abnormal changes of laboratory tests.
4. Compliance: In the 134 eligible cases of patients, 9 (6.7%) claimed that the drug was “very easy to take, ” while 75 (56.0%) reported that the drug was “easy to take.” The cases who reported the drug “very easy to take” and “easy to take” combined to be 62.7%, while those who claimed “ordinary” totaled to be 43 (32.1%). In contrast, 6 (4.5%) claimed that AZM capsules were “difficult to take” and one (0.7%) responded that the capsules were “impossible to take”.
The findings presented above support the conclusion that administration of AZM at a reference dosage of 10 mg/kg, once daily, for 3 days is a useful therapeutic regimen in the treatment of ordinary pediatric infections.