Pharmacokinetic and clinical studies with azithromycin (fine granule) in the pediatric field

Azithromycin (AZM) in 10% fine granules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.5% 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 18 patients and in urine samples from 17 patients to examine of pharmacokinetic characteristics of AZM. 1. Absorption and excretion : C_max's in 16 patients who received 10 mg/kg and 2 patients who received 20 mg/kg were 0.29±0.24 µg/ml and 0.75 µg/ml, respectively, while T 1/2's were 42.0µ 11.8 hours for the former and 51.3 hours for the latter. AUC_0∼∞'s were 10.72± 5.00 µg · hr/ml in the former and 28.83 µg · hr/ml in the latter. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 10 mg/kg AZM in 14 patients, while it peaked at 24 to 48 hours in the patients who received 20 mg/kg. Urinary recovery rates in the first 120 hours after the start were 9.1 ± 2.6% for 10 mg/kg and 10.8 ± 3.4% for 20 mg/kg. 2. Clinical efficacy: The study received 619 entries and 564 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 94.3% in 246 cases where pathogens were identified, classified as Group A. The efficacy rate was 90.7% for the remaining 321 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 92.2%. For the 116 cases where the patients had failed to respond to previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 94.0%. 3. Adverse reactions and abnormal laboratory tests: Incidents of diarrhea, soft stool, skin rashes, or vomiting were found in 15 patients (2.5%) of 596 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 15 patients including 4 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 23 patients (5.6%), increase in eosinophils in 28 (7.1%), increase in platelet count in 2 (0.5%), decrease in platelet count in 1 (0.3%), elevation of GOT in 3 (0.8%), and elevation of GPT in 6 (1.6%). 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 : 614 cases of patients were counted as eligible for evaluation, excluding 14 cases claiming “unknown.” Of 600 cases, 47 (7.8%) claimed that the drug was “very easy to take,” while 312 (52.0%) reported that the drug was “easy to take.” The cases who reported the drug to be “very easy to take” and “easy to take” combined to be 59.8%, while those who claimed “ordinary” totaled to be 217 (36.2%). In contrast, 18 (3.0%) claimed that AZM fine granules were “difficult to take” and 6 (1.0%) responded that the fine granules 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.