부산대학교 도서관

Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals.Informed consents from legal representatives were obtained prior to the study.1. Clinical efficacyTwo-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases. However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease.In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1 %.As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections. The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable β-lactams. On 32 cases with S. pneumoniae infection, the efficacy rate of CFLP was 100.0%. In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8%. In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276). Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia.As for bacteriological responses, eradication rates were 95.2% (177/186) in total. Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae. Against Gramnegative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis.In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases. In these cases, the eradication rate was 98.1% (52/53).2. PharmacokineticsCFLP was intravenously administered to 12 subjects at doses of 20 to 40 mg (potency)/kg. In 9 subjects aged more than 12 months, maximum serum levels (Cmax), T1/2β and AUC of CFLP were 155.3±9.8μg/ml, 1.43±0.18 hours and 111.7±15.0μg·hr/ml, respectively, when a dose of 20mg (potency)/kg was used. In 2 subjects aged not more than 12 months, the mean Cmax, T 1/2β and AUC were 153μg/ml, 1.6 hour and 81μgEhr/ml, respectively, at a dose of 20 mg(potency)/kg. The mean Cmax, T 1/2β and AUC were 332μg/ml, 0.93 hours and 157.3μgEhr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg.In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413±512, 1471±524, and 470±115μg/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary exeretion rate of 61.4±6.3%. In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770μg/ml in 0-2 and 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1%.