We conducted a pharmacokinetic and clinical study on cefpirome (HR 810, CPR), an aminothiazolylmethoxyiminoacetamido cephalosporin (ATOIC), and obtained the following results. 1. Concentrations in blood/excretion in urine. We studied pharmacokinetic in children upon intravenous bolus injections and 30-minute and 1-hour intravenous drip infusions in single dosages of 10, 20 and 40 mg/kg, and obtained virtually the same results as those found in adult subjects. Upon intravenous bolus injections, mean blood concentrations 30 minutes after administration of 10, 20, and 40 mg/kg were 26.1, 47.8, and 82.8 mug/ml, respectively, and half-lives were 1.13, 1.43, and 1.26 hours, respectively. Upon 30-minute intravenous drip infusion, mean blood concentrations on completion of the drip infusions of 10, 20, and 40 mg/kg were 43.2, 106.9, and 163.0 mug/ml, respectively, and half-lives were 1.15, 1.09, and 1.15 hours, respectively. In addition, upon 1-hour intravenous drip infusion, mean blood concentrations on completion of infusion were 27.1 mug/ml for 10 mg/kg and 47.5 mug/ml for 20 mg/kg, and half-lives were 1.09 and 1.40 hours, respectively. A clear dose response was observed at all dosages for either administration method. Mean excretion rates in urine in the first 8 hours after administration were 60.6-71.1% upon intravenous bolus injections of 10-40 mg/kg, and upon intravenous drip infusion, the values were 50.2-83.8% for administration of 10-40 mg/kg 6 or 7 hours after completion of drip infusion. 2. Concentrations in the cerebrospinal fluid. Penetration into the cerebrospinal fluid was studied in 2 subjects, and a concentration of 0.28-5.19 mug/ml was observed upon administration of 50 mg/kg, a moderate degree of penetration compared to the penetration of cephalosporins of group 5 studied up to now. 3. Clinical results. Evaluation of clinical effects of CPR on various types of bacterial infections was conducted in 56 subjects, excluding 3 subjects who had diseases which were excluded from the study. The breakdown was as follows: 3 cases of meningitis, 1 case of septicemia, 25 cases of bronchial pneumonia, 1 case each of tonsillitis and infection of the external acoustic meatus, 2 cases each of scarlet fever and phlegmon, 8 cases each of lymphadenitis and urinary tract infections, and 5 cases of staphylococcal scalded skin syndrome. Results of excellent or good were obtained in 54 subjects for an efficacy rate of 96.4%. There were 6 cases of mixed infections (2 cases of Haemophilus influenzae + Staphylococcus aureus, 1 case each of H. influenzae + Streptococcus pyogenes and H. influenzae + Branhamella catarrhalis, and 2 cases of H. influenzae + Streptococcus pneumoniae), 37 cases of single infections, 22 cases of Gram-positive cocci (12 cases of S. aureus, 4 cases of S. pyogenes, and 6 cases of S. pneumoniae), and 15 cases of Gram-negative bacilli (1 case each of B. catarrhalis, Proteus mirabilis, Haemophilus parainfluenzae, Pseudomonas fluorescens, 6 cases of H. influenzae and 5 cases of Escherichia coli). Causative bacteria were confirmed in 43 of 56 cases, eradication of the bacteria was observed during the course of the study in 40 cases, excluding 1 case each of single infections with S. aureus, S. pneumoniae, and P. fluorescens which were unevaluable, thus an eradication rate of 100% was obtained. From these clinical results according to individual types of bacteria isolated, it appears that CPR was effective in all cases except pneumonia resulting from S. pneumoniae, for a total of 42 of 43 cases with an efficacy rate of 97.7%. 4. Side effects and clinical laboratory findings. A study of safety was conducted on a total of 59 subjects, including 3 subjects with mycoplasmal pneumonia who were excluded. Only few cases of side effects were observed, with only 1 case of each drug fever and diarrhea. In clinical laboratory tests, elevated GOT and GPT and eosinophilia were observed to the same extent as for other group 5 cephalosporins, and an extremely small number of cases of abnormalities such as leukopenia and thrombocytosis was observed. The above results indicate that CPR, which has the outstanding antibacterial properties of group 5 cephalosporins, with an increased practical value against Enterococcus faecalis, and an antibacterial activity against S. aureus comparable to that of old-type cephem preparations, appears to be quite useful as a drug in the treatment of multiple bacterial infections and as replacement in cases where other antibacterial drugs are ineffective.
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