Studies on sultamicillin in the field of pediatrics
Nakamura, H.; Miyazu, M.; Kasai, K.; Iwai, N.; Taneda, Y.
Japanese Journal of Antibiotics 41(12): 1874-1894
1988
ISSN/ISBN: 0368-2781 PMID: 3249361 Document Number: 316008
Pharmacokinetic and clinical studies on sultamicillin (SBTPC) were carried out in the field of pediatrics. 1. Absorption and excretion A crossover study with a single oral administration of 10 mg/kg of SBTPC in fasting and after meal, and that with 10 mg/kg and 20 mg/kg of SBTPC after meal were carried out in 11 children (5 .apprx. 15 years) and in 6 children (8 .apprx. 15 years), respectively. Serum levels and urinary excretion of sulbactam (SBT) and ampicillin (ABPC) were determined. Mean serum concentrations of ABPC after oral administration of 10 mg/kg of SBTPC with in fasting or after meal, in the former study, peaked at 4.75.+-.1.97 .mu.g/ml in 1 hour and declined with a mean half-life of 0.81.+-.0.18 hour and the mean serum concentration of ABPC at 6 hours after administration was 0.06.+-.0.07 .mu.g/ml. Mean serum concentration of ABPC study in the latter peaked at 2.95.+-.0.79 .mu.g/ml in 1 hour, and declined with a mean half-life of 1.35.+-.0.43 hours, and the mean serum concentration of ABPC at 6 hours was 0.22.+-.0.13 .mu.g/ml. Mean urinary recovery rates of ABPC in 6 hours after administration were 54.5.+-.17.6% in the former study, and 63.2.+-.14.3% in the latter. These results suggested a delay of absorption with meal. Mean serum concentrations of ABPC after oral administration of 10 mg/kg or 20 mg/kg of SBTPC after meal, in the former study, were 3.10.+-.0.72 .mu.g/ml at 1 hour and declined with a half-life of 1.22.+-.0.32 hours, and those of ABPC were 0.22.+-.0.12 .mu.g/ml at 6 hours, and they were 6.46.+-.1.57 .mu.g/ml, 1.48.+-.0.51 hours and 0.55.+-.0.40 .mu.g/ml, respectively in the latter study. Mean urinary recovery rates of ABPC in 6 hours, were 50.4.+-.10.2% in the former study and 57.7.+-.11.4%, in the latter. A dose response was observed with time course of mean serum concentrations. Mean serum concentrations of SBT were lower than those of ABPC, and they declined in a similar manner. The mean urinary recovery rate of SBT was similar or lower than that of ABPC. 2. Clinical study SBTPC was used for the treatment of a total of 38 pediatric patients with ages 6 months to 11 years and it's clinical effectiveness, bacteriological efficacy and adverse effects were evaluated. Clinical efficacies in 8 patients with acute purulent tonsillitis, 22 with acute pneumonia, 1 each with acute pharyngitis, acute purulent otitis media, acute purulent parotitis and impetigo were judged to be excellent in 28 cases and good in 6 cases with an efficacy ratio of 100.0%. Clinical efficacies in 5 patients with infections caused by .beta.-lactamase producing strains were judged to be excellent or good in all cases. Bacteriological efficacies of SBTPC were assessed on 2 strains of Staphylococcus-aureus (.beta.-lactamase producing strains), 3 strains of Streptococcus-pyogenes, 2 strains of Streptococcus-pneumoniae and .beta.-Streptococcus, 9 strains of Haemophilus-influenzae (2 .beta.-lactamase producing strains, 7 .beta.-lactamase non-producing strains) and 1 strain of Haemophilus-parainfluenzae (.beta.-lactamase producing strain). All strains except 1 strain of S. aureus (.beta.-lactamase producing strain) which decreased in number, 1 strain of b-Streptococcus which persisted and 1 strain of H. influenzae (b-lactmase non-producing strain) which decreased in number, were eradicated with a bacteriological eradication rate of 84.2%. Only 1 patient complained of diarrhea which was suspected to be related to the drug. No other side effect was reported. Abnormalities in laboratory test values included 3 cases of eosinophila, 1 case of elevated platelet number and 1 case of GOT elevation. The above results suggested that SBTPC was a useful drug with a preferable safety profile in the treatment of pediatric patients with infectious diseases caused by .beta.-lactamase producing strains as well as non-.beta.-lactamase producing strains.