PHARMACOKINETIC, BACTERIOLOGICAL AND CLINICAL STUDIES OF SULBACTAM/AMPICILLIN IN PEDIATRIC PATIENTS

Abstract

Plasma and urine concentrations of sulbactam (SBT) and ampicillin (ABPC) were determined following bolus administration of injectable SBT/ABPC combined in a fixed ratio of 1: 2 to 6 pediatric patients, 3 at a dose of 30mg/kg and the other 3 at 60mg/kg. Clinical and bacteriological efficacies of SBT/ABPC were evaluated in a total of 65 patients composed of 45 cases with pneumonia, 3 cases each with bronchitis, urinary tract infections, staphylococcal scalded skin syndrome, purulent lymphadenitis, 2 cases each with tonsillitis, pleuropneumonia, phlegmon and 1 case each with pyothorax, submaxillaritis. The dosage used was 101.2mg/kg daily given in 3 or 4 divided doses (t. i. d. in 24 patients and q. i. d. in 41 patients) by bolus intravenous injection for 7 days on an average. Side effects and effects on clinical laboratory parameters were monitored in the 65 patients. The results of these evaluations are summarized as follows.
1. Mean serum concentrations of SBT and ABPC in 3 children each given an intravenous bolus injection of 30mg/kg and other 3 each given 60mg/kg reached peak levels at 5 minutes after administration with values of 49.8 and 90.3μg/ml, respectively, for SBT and 99.8 and 189.7μg/ml, respectively, for ABPC. The latter values were about twice as high as SBT, and both were dose-related. Mean half-lives were 0.889 hour for SBT and 0.857 hour for ABPC in the 30mg/kg group and 0.882 hour for SBT and 0.834 hour of ABPC in the 60mg/kg group, showing similarities between the 2 dosage groups as well as between SBT and ABPC.
2. Mean urine concentrations in the 2 groups mentioned above were the highest for both SBT and ABPC during the first 2 hours after administration, with values of 1,677μg/ml for SBT and 2,730μg/ml for ABPC in the 30mg/kg group and 2,693μg/ml and 3,623μg/ml, respectively, in the 60mg/kg group. Mean recovery rates in urine in the first 6 hours were 72.4% for SBT and 56.8% for ABPC in the low dosage group and 72.7% and 52.0%, respectively, in the high dosage group. In the 2 groups, the amounts of ABPC recovered were less than those of SBT.
3. Clinical efficacies of SBT/ABPC in 65 patients with various bacterial infections were excellent or good in 62 (95.4%) patients.
4. The bacteriological efficacy was evaluable with 10 patients. The pathogenic bacteria were eradicated in 9 patients and the efficacy rate was 90%.
5. In a total of 65 patients administered with SBT/ABPC, eruption as side effect of the drug occurred in 1 patient (1.5%), laboratory parameter abnormalities found were granulocytopenia in 1 patient (1.7%), eosinophilia in 4 (6.9%), thrombocytosis in 2 (4.3%), thrombocytopenia in 1 (2.1%), elevation of GOT in 2 (3.7%), elevation of GOT and GPT in 2 (3.7%) and elevation of LDH in 1 (2.4%). There was no case with abnormal values of Al-P, BUN or creatinine.