[Pharmacokinetic and clinical studies on meropenem].

Pharmacokinetic and clinical studies on meropenem (MEPM, SM-7338), a new developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of MEPM was studied in 9 children using doses of 10 mg/kg and 20 mg/kg by a 30 minute-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 28.4 and 43.0 micrograms/ml, and 0.70 and 0.80 hours, respectively. Their urinary recovery rates were 42.5 to 67.6% and 29.9 to 62.6%, respectively. Cerebrospinal fluid levels and penetration rates of MEPM in a patient with purulent meningitis were 0.66 to 4.01 micrograms/ml and 1.6 to 12.2%, respectively. 2. Clinical study: Forty-nine patients were treated with MEPM at doses exceeding 100 mg/kg/day with purulent meningitis and 30 to 60 mg/kg/day with other infections. MEPM gave "excellent" or "good" responses in 48 cases, an efficacy rate of 98.0%. Only one patient with subdural abscess showed fair response. Diarrhea and rash were observed in 1 case each. Abnormal laboratory test results were noted in 5 patients including elevation of GOT, GPT and eosinophils. In no cases the treatment had to be discontinued.

[Pharmacokinetic and clinical studies on panipenem/betamipron in the pediatric field].

UNLABELLED: Panipenem/betamipron (PAPM/BP), one of the carbapenems, was studied for its absorption and excretion, and clinical efficacy. The following is a summary of the results: 1. Absorption and excretion: Fourteen patients with their ages between 2 years and 14 years were administered with PAPM/BP 10 mg/kg, 20 mg/kg or 30 mg/kg, in 30-minute intravenous drip infusion. Maximum serum levels of PAPM, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg of PAPM/BP, were 27.37 micrograms/ml, 59.3 micrograms/ml, 91.7 micrograms/ml, respectively, at the end of infusion. The half-lives of the 3 dose levels were all within 0.90-0.96 hour. Mean peak serum levels of BP, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 21.77 micrograms/ml, 35.29 micrograms/ml, 50.08 micrograms/ml, respectively, with half-lives of 0.55-0.63 hour. Urinary recovery rates of PAPM in the first 8 hours after administration at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 15.9-31.1%, 15.3-36.9%, 11.0-40.5%, respectively, and those of BP during the same time were 33.1-79.1%, 41.3-93.4%, 12.9-94.4%, respectively. 2. CLINICAL RESULTS: Thirty-nine patients, including 2 with purulent meningitis, 1 with septicemia (suspect), 18 with acute pneumonia, 5 with bronchiolitis, 2 with tonsillitis (unable to receive oral antibiotics), 3 with cervical purulent lymphadenitis, 2 with bacterial enteritis, 6 with urinary tract infections were treated with PAPM/BP at dose levels of 30-100 mg/kg/day. Clinical responses in the patients were excellent or good. Even 2 patients with purulent meningitis were treated with PAPM/BP at dose levels of no less than 20 mg/kg x 3 and 33 mg/kg x 3. Most of respiratory and urinary tract infection cases of moderate severities were treated at dose levels of 30-60 mg/kg/day, i.e., 10 mg/kg x 3 or 20 mg/kg x 3. No adverse reaction was observed. One patient suffered from frequent watery diarrhea but the drug was continued to be administered and the patient recovered quickly. Abnormal laboratory findings were noted, in 2 cases with elevation of platelet, in 1 case with elevation of GOT, in 1 case with elevation of monocyte, in 1 with eosinophilia, in 1 with eosinophilia and decrease in platelet count, in 1 with eosinophilia and elevation of GOT and in 2 with elevation of GOT and GPT, but these abnormalities in the 9 cases were slight and transient.

[Bacteriological, pharmacokinetic and clinical studies of 5% and 10% granules of cefdinir in the pediatric field].

Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC). MIC80's of CFDN against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, B. catarrhalis, K. pneumoniae and E. coli were 0.78, 0.20, less than or equal to 0.025, 0.39, 0.10, 0.20 and 0.10 micrograms/ml, respectively. These results show that CFDN has high antibacterial activities against these organisms. MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX. As for antibacterial activities against Gram-negative bacteria (GNB), the MIC80 of CFIX against H. influenzae was 0.05 micrograms/ml, which was slightly lower than that of CFDN. THe MIC80's of CFDN against other GNB were similar to those of CFIX. 2. Absorption and excretion Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined. The data on CFDN 10% granules were similar to those on CFDN 5% granules. At a dose of 3 mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12 micrograms/ml with 5% granules and from 0.50 to 1.15 micrograms/ml with 10% granules at 2 to 3 hours after dosing. At a dose of 6 mg/kg, peak concentrations were 0.66-2.06 micrograms/ml and 0.70-1.52 micrograms/ml with 5% granules and with 10% granules, respectively. At 8 hours after dosing, blood concentrations were 0.04-0.54 micrograms/ml at 3 mg/kg and 0.06-0.27 micrograms/ml at 6 mg/kg. Blood half-lives were 1.33-4.36 hours at 3 mg/kg and 1.14-3.27 hours at 6 mg/kg. AUC's were 1.7-11.0 micrograms.hr/ml with 3 mg/kg and 2.4-8.7 micrograms.hr/ml with 6 mg/kg. With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T1/2's and AUC's were 0.79-1.88 micrograms/ml, 0.20 micrograms/ml, 1.54-2.72 hours, and 5.2 micrograms.hr/ml, respectively. Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3 mg/kg and 6.08-25.5% with 6 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetic and clinical evaluation of cefpirome in the pediatric field].

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 micrograms/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 micrograms/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 micrograms/ml for 10 mg/kg and 47.5 micrograms/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 micrograms/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%.(ABSTRACT TRUNCATED AT 400 WORDS)