MR and CT findings of craniopharyngioma during and after radiation therapy.

Long-term changes in craniopharyngioma treated with radiation therapy (RT) were investigated by computed tomography (CT) and/ or magnetic resonance (MR) imaging. Eight patients with craniopharyngioma were treated with incomplete resection or conservative surgical intervention followed by postoperative RT. The periods of tumor shrinkage were often long and varied (range: 6-68 months, mean: 29.1 months). Temporary enlargement of the solid component of a tumor usually occurs during RT and does not represent tumor progression. Cystic enlargement also occurs sometimes comparatively early after RT, and enlarged cysts often shrink with no treatment or with conservative treatment. These changes should be differentiated from tumor recurrence, with careful follow-up. After shrinkage, small solid or cystic nodules enhanced with contrast medium often remain. Long-term follow-up is necessary to differentiate uncontrolled tumors from controlled tumors with imaging modalities.

[Pharmacokinetic and clinical studies of S-1108 in the pediatric field. Pediatric Study Group of S-1108].

S-1108 in granules, a new oral cephem antibiotic, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained. 1. Pharmacokinetics S-1108 was administered at single doses of 2, 3, 4, 6 mg/kg orally and the following results were obtained on Cmax, T 1/2 and AUC, respectively: Cmax: 0.79, 1.03, 1.39, 1.06 micrograms/ml, T 1/2: 1.28 +/- 0.40, 1.27 +/- 0.65, 1.10 +/- 0.29, 1.83 hrs., AUC: 2.65 +/- 0.63, 3.99 +/- 2.77, 5.25 +/- 1.83, 5.15 micrograms.hr/ml. These values indicated a dose-dependent pharmacokinetic behavior. Urinary recovery rates were 12.5-30.0% in the first 8(6) hours after administration. 2. Clinical results The clinical efficacy of S-1108 was evaluated in 456 patients with various infections. S-1108 was administered at a dose of 2-4 mg/kg three time a day to most patients. The overall clinical efficacy rate was 95.0%. In 294 cases with identified causative pathogen, the clinical efficacy rate was 96.9%, and the bacteriological eradication rate was 89.0%. Side effects occurred in 18 (3.23%) of 558 patients subjected to safety analyses. The main side effect was diarrhea but those side effects were mild and reversible. Abnormal laboratory test results were observed in 25 cases, (eosinophilia and elevated GOT and GPT). These abnormalities were not dose-dependent and also seen with other cephems to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, S-1108 is considered to be very useful at a standard dose of 2-4 mg/kg t.i.d. against most infections encountered in the pediatric field out-patient clinic.

[Pharmacokinetic and clinical studies of SY5555 in the pediatric field. Pediatric Study Group of SY5555].

SY5555, a new oral penem, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics Pharmacokinetics of SY5555 dry syrup (powder which is dissolved before use) was investigated in 64 children. At a dose level of 3 mg (potency)/kg, Cmax and T1/2 were 0.33 micrograms/ml and 0.95 hours (n = 1), respectively, in the non-fasting state. At a dose level of 5 mg/kg Cmax and T1/2 were 2.09 +/- 1.25 micrograms/ml and 1.20 +/- 1.07 hours, respectively, in the fasting state, and were 1.21 +/- 0.70 micrograms/ml and 1.33 +/- 0.90 hours, respectively, in the non-fasting state. At a dose level of 10 mg/kg, Cmax and T1/2 were 2.96 +/- 1.89 micrograms/ml and 0.89 +/- 0.43 hours, respectively, in the fasting state, and were 2.45 +/- 1.37 micrograms/ml and 1.17 +/- 0.53 hours, respectively, in the non-fasting state. At a dose level of 15 mg/kg, Cmax and T1/2 were 4.30 +/- 2.15 micrograms/ml and 0.82 +/- 0.09 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that plasma concentration of the drug depended on dose levels. Urinary recovery rates in the first 6 hours were 1.71% (n = 1) in the non-fasting state at a dose level of 3 mg/kg, 4.13 +/- 1.40% in the fasting state and 4.17 +/- 3.29% in the fasting and the non-fasting state, respectively at a dose level of 5 mg/kg, and 6.02% (n = 1) and 4.64 +/- 2.81%, respectively, at a dose level of 10 mg/kg. At a dose level of 15 mg/kg, urinary recovery rate in the first 6 hours was 7.97% (n = 2) in the non-fasting state. 2. Clinical results 1) Dry syrup The clinical efficacy of the SY5555 dry syrup was evaluated in 506 cases. SY5555 was administered at daily doses of 15-30 mg/kg divided into 3 equal doses to most patients. Daily doses of 12- < 18 mg/kg were given to 46.6% of the patients. The overall clinical efficacy rate was 92.9%, and this drug was effective in 93.0% of the 301 patients for whom the causative pathogens were identified, and in 92.7% of the 205 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of 12 - < 18 mg/kg was 94.5% similar to those obtained at daily doses of 18- < 27 mg/kg (91.7%) or 27- < 33 mg/kg (91.3%). The bacteriological eradication rate was 82.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

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

Pharmacokinetic and clinical evaluations of cefpirome (CPR), a newly developed cephalosporin, were performed in the field of pediatrics. The results are summarized as follows. 1. Peak serum concentrations of CPR after a dose of 20 mg/kg via 30 minutes and that via 60 minutes intravenous drip infusion and a dose of 40 mg/kg via 60 minutes intravenous drip infusion were 80.8, 63.7 and 128.8 micrograms/ml, respectively, with half-lives being 1.41, 1.28 and 1.79 hours, respectively. Urinary excretion rates for CPR in the first 6 hours after administration ranged 66.7-77.1%. 2. The clinical efficacy rate in pediatric infections obtained at daily dose levels ranging 55.6-166.7 mg/kg was 95.7%. 3. The eradication rate for 22 strains identified in the study was 95.5%. 4. Side effects were found in 2 cases of diarrhea. The abnormal laboratory test results were observed in 5 cases with 7 test items (increased number of platelets; 2 cases, increased activity of GOT; 2 cases and increased activity of GPT; 1 case). According to these results, CPR was considered to be a useful antimicrobial agent in pediatric infections.

[Clinical studies on cefdinir granules in pediatric field].

Cefdinir (CFDN, FK482) granules, a new oral antibiotic for children, were given to children with infections. The results obtained are summarized as follows. 1. The plasma level of CFDN peaked at 0.38-0.88 microgram/ml in 2-3 hours after administration of the drug at a dose of 3 mg/kg. Meanwhile, the plasma level peaked at 1.85 micrograms/ml in 3 hours after administration of 6 mg/kg. The plasma level was higher in the 6 mg/kg group than that in the 3 mg/kg group, thus a dose response was clearly observed. 2. The 8 hour urinary excretion accounted for 10.3-17.4% of administered amount of the drug in children with 3-6 mg/kg dosage. 3. CFDN granules were administered to a total of 42 children with upper or lower airway infections or with urinary tract infections at daily doses of 9.0-20.7 mg/kg in 3 divided portions. The clinical efficacy was "excellent" in 28 patients, "good" in 13, and "fair" in 1, hence an efficacy rate of 97.6% was obtained. 4. Bacteria identified from various diseases were 29 strains of 9 species, and the eradication rate was 82.8%. 5. No. side effects were noted in any of the children. Laboratory test results showed an abnormality in 1 case each with a rise of platelet count and eosinophilia.

[Pharmacokinetic, bacteriological and clinical studies in the pediatric field on norfloxacin].

We have evaluated norfloxacin (NFLX), a fluoroquinolone agent, in tablet form for its efficacy and safety in the field of pediatrics. 1. Mean serum concentrations of NFLX following oral administration to 3 children at dose levels of 3.2 mg/kg, 3.7 mg/kg and 5.4 mg/kg were, respectively, 0.7 microgram/ml, 0.18 microgram/ml and 0.64 microgram/ml at 2-4 hours. Mean serum half-lives (T1/2) of NFLX were 2.5-2.9 hours and mean urinary recovery rates in the first 6 hours after administrations were 7.1-30.7%, depending on dose levels. 2. Antibacterial activities of NFLX against clinically isolated 30 organisms from children were determined. MIC of NFLX against Staphylococcus aureus was similar to that of ABPC, 0.39-25 micrograms/ml. MIC of NFLX against Escherichia coli was approximately less than or equal to 0.10 microgram/ml. This MIC value was lower than other antibiotics. MIC of NFLX against Vibrio parahaemolyticus was less than or equal to 0.10 microgram/ml. 3. NFLX was administered to 30 patients (7 patients with Salmonella enteritis, 7 patients with Campylobacter enteritis, 5 patients with other enteritis, 1 patient with bacillary dysentery, 8 patients with urinary tract infection, 2 patients with skin soft tissue infection). The clinical responses of these 30 patients were as follows; excellent: 24 patients, good: 4 patients. The efficacy rate was 93.3%. 4. The bacteriological efficacy rate of NFLX against clinically isolated 29 organisms from children was 75.9%, including 3 cases in which other antimicrobial agents had been ineffective. Especially against Salmonella spp. was superior to other agents tested. 5. Neither clinical adverse reaction nor abnormal laboratory data was found in any of these 33 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Studies of aztreonam in neonates].

Absorption and excretion of aztreonam (AZT) in neonates were studied and its clinical evaluation in 10 cases of neonates was performed using 1 hour intravenous drip infusion. 1. Serum concentrations of AZT in 7 neonates younger than 11 days of age were lower than those in infants. 2. Serum concentrations of AZT in 5 neonates given 20 mg/kg reached their peaks at the end of intravenous drip infusion with an average value of 45.8 +/- 10.41 micrograms/ml, and T 1/2 was 2.77 +/- 0.32 hours on the average. 3. Serum concentrations of AZT in 2 neonates given AZT 25 mg/kg reached their peaks at the end of intravenous drip infusion at 31.1 and 33.4 micrograms/ml with little difference from the 20 mg/kg group. Half-lives of serum AZT in the 2 cases were 1.87 hours and 3.23 hours, respectively. 4. Urinary excretion rates of AZT in 7 neonates younger than 11 days of age in the first 6 to 8 hours after the administration were 18.8 to 50.0%, or 31.7% on the average, which was lower than the average excretion rate found with infants. 5. All the cases given AZT showed clinical results rated better than "effective". Effect of AZT was excellent on 3 UTI cases caused by Escherichia coli and Klebsiella pneumoniae, but bacterial replacement (superinfection) of Enterococcus faecalis was observed when AZT was administered. 6. Transient elevations of GOT and GPT were seen in 2 cases when AZT administration was continued at length. Clinical side effect was not observed. 7. The most appropriate dosage and administration scheme of AZT against Gram-negative infections in neonates seems to be 40-60 mg/kg/day, b.i.d. or t.i.d.

[Evaluation of norfloxacin in the pediatric field. Pediatric Study Group for Norfloxacin].

Norfloxacin (NFLX, AM-715), a new quinolone antibiotic agent, was evaluated clinically and bacteriologically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Incidence of NFLX-resistant strains (MIC over 12.5 micrograms/ml) isolated from children with various infections was 1.6% (8/512). One resistant strain was observed among 45 isolates of Staphylococcus aureus, and none among 30 isolates of Pseudomonas aeruginosa. 2. After single oral administration of 1.5-2.9, 3.0-4.8 and 5.1-6.1 mg/kg NFLX in tablet form at fasting, mean peak values of serum concentration of 0.37, 0.56, 0.92 micrograms/ml, T1/2 of 2.5, 2.6, 2.6 hours and urinary recovery rates in 8 hours at 25.3, 25.3, 27.1% were observed, respectively. 3. Clinical effects were studied chiefly in intestinal and urinary tract infections. Among 317 patients from whom pathogens had been isolated, responses to the treatment were excellent in 187, good in 79, fair in 9, poor in 7, and unknown in 35 cases. The overall efficacy rate was 94.3% (266/282) and the efficacy rate for excellent responses was 70.3% (187/266). Among all the 406 patients treated, including those with undetermined pathogens, responses were excellent in 233, good in 106, fair in 11, poor in 11, and unknown in 45 cases. The overall efficacy rate was 93.9% (339/361). 4. Clinical effects of NFLX classified by diseases with identified pathogens were 81.8% (9/11) for acute pneumonia, 80.8% (21/26) for other respiratory infections, 95.8% (23/24) for bacillary dysentery, 98.6% (70/71) for Campylobacter enteritis, 100% (24/24) for Salmonella enteritis, 100% (6/6) for other acute enteritis and 98.1% (104/106) for urinary tract infections. Including other infections as high as 94.3% (266/282) of efficacy rate was obtained in total. There was no significant difference in NFLX efficacies between unidentified and identified pathogens. Thus, the total clinical efficacy rate was 93.9% (339/361). 5. The total eradication rate of 325 pathogens evaluable was 84.3%, with identical eradication rates for Gram-positive cocci (GPC) (43/51) and for Gram-negative rods (GNR) (231/274). 6. The optimal daily dose of NFLX seemed to be in a range between 6.0 and 12.0 mg/kg, and the optimal duration of treatment to be 7 days for children over 5 years old. 7. The clinical efficacy in treating P. aeruginosa infections in 12 patients was 100% (11/11) and the eradication rate was 83.3% (10/12).(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetic and clinical studies on cefmenoxime in newborn infants].

Pharmacokinetic and clinical studies on cefmenoxime (CMX) were performed in infants given by the drug intravenous drip infusion or one shot intravenous injection. The results obtained are summarized as follows. 1. Serum concentrations of CMX in infants given CMX at 10 mg/kg by intravenous drip infusion peaked at 12.0 to 26.5 micrograms/ml at the termination of the administration, and the levels were 8.62 to 26.3 micrograms/ml in 1 hour after dosing. Half-lives were 2.9 to 3.8 hours. 2. Serum concentrations of CMX in infants given the drug at 20 mg/kg by the same manner for 30 minutes to 1 hour peaked at 40.8 to 74.3 micrograms/ml at the termination of the administration, and drug levels decreased to 17.6 to 45.4 micrograms/ml in 1 hour after dosing. Half-lives were 0.8 to 2.7 hours. Those of CMX in infants given the same dose by one shot intravenous injection peaked at 61.7 to 90.6 micrograms/ml immediately after dosing, and decreased to 22.3 to 48.2 micrograms/ml at 1 hour. Half-lives were 1.2 to 2.7 hours. 3. As described above, dose-response was observed between the doses of 10 mg/kg and 20 mg/kg. 4. Urinary recovery rates were 2.6 to 47.7% during the first 6-8 hours in most of 1 to 2 day-old infants, and 17.6 to 72.4% in most of 5 day-old or older ones. 5. Twelve infants with various bacterial infections were given CMX by intravenous injection or drip infusion. Clinical efficacies of CMX were excellent or good in all the 9 infants with pneumonia, septicemia, amniotic fluid-aspiration syndrome or intra-placental infection etc., while 3 cases were excluded: 1 each with congenital syphilis (0 day old), acute bronchitis (56 days old) and whooping cough (54 days old). 6. Dosages of CMX used in the present study were 33 to 79 mg/kg/day, and durations of treatment ranged from 4 to 13 days. No abnormal laboratory test values were observed. Moreover, neither systemic nor local adverse effects attributable to CMX were encountered in any of the infants.

[Clinical studies on cefteram pivoxil granules in pediatrics].

A newly developed cephalosporin, cefteram pivoxil (CFTM-PI, T-2588), was evaluated clinically in 40 patients. A pharmacokinetic study was also performed with 8 patients. CFTM-PI was administered as granules. One patient was given CFTM-PI at a dose of 1.5 mg/kg, each of 3 patients was given the drug at a dose of 3 mg/kg and each of 4 patients at a dose of 6 mg/kg. In most cases, serum concentrations of CFTM were determined at 2, 3, 4, and 6 hours after dosing. Urinary concentrations of CFTM were measured for urinary samples collected during periods of 0-2, 2-4, 4-6 and 6-8 hours after dosing. CFTM was assayed using the disk or the cup method using Klebsiella pneumoniae ATCC 10031 as the test organism. The clinical evaluation was conducted in 40 children including 13 patients of acute tonsillitis, 10 of acute lacunar tonsillitis, 10 of scarlet fever, 2 of acute bronchitis, 2 of pneumonia, and 1 each of pneumonia with enteritis, phlegmon and urinary tract infection. The patients were from 4 months to 13 years old. Daily doses were from 8.7 to 12 mg/kg. After CFTM-PI administration in doses 1.5 mg/kg, 3 mg/kg and 6 mg/kg, peak serum concentrations of CFTM were 0.38 microgram/ml, 0.73-2.25 micrograms/ml and 1.2-2.9 micrograms/ml, respectively, and half-lives were 1.55, 0.95-2.30 and 0.80-2.72 hours, respectively. Urinary excretion rates up to 6 or 8 hours after dosing were 10.8-24.7%. Clinical efficacies of CFTM-PI in 40 patients were "excellent" in 27 children, "good" in 12 children and "fair" in 1 with an efficacy rate of 97.5%. Twenty seven strains of causative organisms, including 15 strains of Streptococcus pyogenes, 1 of Escherichia coli, 1 of Salmonella 04, 6 of Haemophilus influenzae, 1 of Haemophilus parainfluenzae and 3 of Branhamella catarrhalis, were isolated. After treatment all strains except 1 strain of B. catarrhalis (unchanged), Salmonella 04 (unknown) and 1 strain of H. parainfluenzae (unknown) were eradicated. Side effects observed clinically were only 1 case of diarrhea. Eosinophilia was observed in 1 case.

[Evaluation of cefpodoxime proxetil in the pediatric field].

Pharmacokinetic and clinical evaluation of cefpodoxime proxetil (CPDX-PR, CS-807) were performed in the field of pediatrics. The obtained results are summarized as follows. 1. Peak serum concentrations of CPDX upon single oral doses of 3.0 mg/kg and 4.4 mg/kg of CPDX-PR were 1.26-1.46 micrograms/ml and 1.45 micrograms/ml, respectively, achieved at 4 hours and 1 hour after administration. Urinary excretion rates for CPDX in the first 8 hours ranged between 28.1 and 30.2%. 2. Clinical efficacy rates for pediatric infections obtained at single dose levels ranging 3 to 6 mg/kg were 97.5%, and that at a single dose of 1 mg/kg were 90.9%. 3. Bacteriological effectiveness was determined in 45 strains identified in recent cases. Eradication rates for these bacteria at dose levels of 3 to 6 mg/kg and 1 mg/kg were 91.3% and 95.5%, respectively. 4. No side effect nor abnormal laboratory test data were found in any of the cases examined. From these results, CPDX-PR appeared to be a useful antibiotic agent in the field of pediatrics.

[Study on cefodizime, a new cephem antibiotic, in the field of pediatrics].

Experimental and clinical study of cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, was done in the field of pediatrics and the results obtained are summarized as follows: 1. Serum levels and urine excretion were examined after 60-minute drip infusion of CDZM at a dose level of 10 mg/kg to 1 patient, at 20 mg/kg to 4 and at 40 mg/kg to 1. Peak levels in serum were 66.3 micrograms/ml for the 10 mg/kg dose occurring 1 hours after the dose, 118.1 micrograms/ml (mean) for 20 mg/kg, 259.2 micrograms/ml for 40 mg/kg, thus a dose-response was observed. T 1/2's (beta phase) were between 1.17 and 1.69 hours. Urinary recovery rates of the drug were between 71.5% and 98.0% in the first 8 hours after administration. 2. The concentration in the cerebrospinal fluid was 0.76 microgram/ml and the serum level was 380.67 micrograms/ml at 15 minutes after intravenous administration of 433 mg of CDZM to a patient with purulent meningitis. 3. The clinical efficacy rate was 95.2% in a total of 21 cases, i.e., 1 purulent meningitis, 10 respiratory tract infection, 3 whooping cough, 5 urinary tract infection, 1 purulent infection of soft tissues and 1 acute thyroiditis. Diarrhea occurred in 1 case as adverse reactions. Abnormal changes in laboratory test results occurred as 1 case each of slightly elevated GOT.GPT and GOT.

[Clinical and pharmacokinetic studies on intravenous administration of sulbactam/ampicillin in pediatrics].

Intravenous administration of sulbactam/ampicillin (SBT/ABPC) was evaluated in pediatric patients. The serum half-lives of both ABPC and SBT were approximately 1 hour following the intravenous injection or intravenous drip infusion of 20-35 mg/kg, and 30-50% of ABPC and 30-70% of SBT were recovered in the urine 6 hours. Cerebrospinal fluid concentrations of ABPC and SBT were 0.76 and 0.68 micrograms/ml, respectively, at 1 hour after intravenous drip infusion of the 58 mg/kg, and concentration ratios of the drugs in cerebrospinal fluid/serum were 6.39 and 5.71%, respectively. Thirty-four pediatric patients were treated with intravenous drip infusion of SBT/ABPC in doses ranging from 54 to 150 mg/kg divided into 3 times a day. The rate of clinical efficacy was 93.5% and the bacterial elimination rate was 92.3%. The synergistic activity of sulbactam with ampicillin was demonstrated against beta-lactamase-producing Staphylococcus aureus and Haemophilus influenzae isolated from patients in the present study. The side effects of SBT/ABPC were observed in 6 patients (5 diarrheas; 1 diarrhea with vomiting) out of 34 patients administered. Eosinophilia (2 patients) and a slight elevation of GOT (1 patient), GPT and LDH (1 patient) were observed. The tolerance to the therapy, however, was good.

[Pharmacokinetic, bacteriological and clinical studies in the pediatric field on clarithromycin].

Pharmacokinetic, bacteriological and clinical studies were carried out on clarithromycin (TE-031, A-56268) in the pediatric field and following results were obtained. 1. Peak concentrations of TE-031 in the serum occurred at 1-2 hours after administration of 10 mg/kg in granular form and at 2 hours after administration of 20 mg/kg in granular form. Half-lives of the drug in serum were 2.5-3.3 hours in cases of 10 mg/kg dosage and 5.5 hour in case of 20 mg/kg dosage. TE-031 tablets were administered in a dosage between 1.7 and 5.0 mg/kg and peak concentrations in the serum occurred at 0.5-2 hours. Half-lives were 2.0-4.3 hours. 2. Urinary recovery rates obtained upon administration of TE-031 granule during the first 6 hours after administration were 20.3-62.9%, while they were 11.6-42.4% with TE-031 tablets. 3. Antibacterial activity of TE-031 against Campylobacter jejuni was equal to that of erythromycin and slightly superior to those of josamycin, midecamycin acetate and rokitamycin. 4. Bacteriological efficacy rate of TE-031 on 8 species of bacteria isolated from various samples was 88.4% and clinical efficacy rate on 66 cases (upper/lower respiratory tract infections, mycoplasmal pneumonia, Campylobacter enteritis, et al.) was 100%. 5. TE-031 was administered in dosages of 6.8-42.3 mg/kg/day (mostly 20-30 mg/kg/day) 3 times a day and lengths of administration ranged from 4 to 15 days. 6. Side effects due to TE-031 were observed in 1 case each of transient symptom and abnormal clinical laboratory test value. According to the above results, TE-031 was recognized as a useful antibiotic for the treatment of infections in the pediatric field.

[Clinical and pharmacokinetic studies on sultamicillin fine granules in pediatrics].

Sultamicillin (SBTPC) is a mutual prodrug of sulbactam (SBT) and ampicillin (ABPC). A study has been performed to evaluate pharmacokinetic properties and clinical usefulness of SBTPC fine granules in the treatment of pediatric infections. After an oral dose of 5-15 mg/kg of SBTPC fine granules, peak serum concentrations of ABPC and SBT were 1.18-3.26 micrograms/ml and 0.97-3.05 micrograms/ml, respectively at 1 hour. Serum half-lives for elimination (T 1/2 (beta] of ABPC and SBT were 0.83-1.83 hours and 0.94-1.71 hours, respectively. Serum concentrations of ABPC at 1-6 hours after an oral administration of SBTPC fine granules were similar to those of SBT. Serum concentrations of ABPC and SBT were proportional to dose levels of SBTPC fine granules. Following oral administrations of 5-15 mg/kg, 33.9-64.8% of ABPC and 38.1-76.6% of SBT were recovered in urine in 6 hours. SBTPC fine granules were administered in a daily dose of approximately 30 mg/kg divided into 3 doses to 14 pediatric patients with bacterial infections. All 14 were cured with 11 excellent and 3 good clinical response to this drug. Microbiological eradication was obtained in 85.7%. beta-Lactamase-producing ABPC-resistant strains were eradicated. Adverse effects including laboratory test values that may be attributed to the administration of SBTPC fine granules were not observed except a treatment episode of diarrhea in 1 patient.

[Pharmacokinetic and clinical studies of ceftizoxime in newborn infants].

Pharmacokinetic and clinical studies of ceftizoxime (CZX) were performed in infants given intravenously. The obtained results are summarized as follows. 1. Serum concentrations of CZX in 2 and 3 day-old mature infants given 20 mg/kg by one shot intravenous injection peaked at 49.0 and 57.9 micrograms/ml in 1 hour and decreased to 14.4 and 24.9 micrograms/ml in 8 hours after dosing, respectively. Half-lives were 3.9 and 5.6 hours, respectively. In 5 day-old or older mature infants, peak serum levels ranged from 20.9 to 38.0 micrograms/ml at 1 hour after the injection. Levels of CZX at 8 hours after injection were 1.31 to 7.32 micrograms/ml. Half-lives were 1.6-3.0 hours in all the infants except one. 2. In a 3 day-old premature infant given the same dose by a bolus intravenous injection, the serum level peaked at 45.7 micrograms/ml in 1 hour after the injection. The level at 8 hours after injection was 15.7 micrograms/ml. The half-life was 4.2 hours. In 5-15 day-old premature infants, half-lives were 2.3-3.1 hours in all the infants except one. 3. Serum concentrations of CZX in 1 and 2 day-old infants given 20 mg/kg by intravenous drip infusion peaked at 49.4 to 115.0 micrograms/ml in 1 hour after dosing. Half-lives were rather long, 4.0 and 5.1 hours, in the 2 infants. 4. Peak serum levels and half-lives tended to be lower and shorter in 5 day-old or older ones than in the 3 day-old or younger infants. 5. No changes in the serum concentration were observed even after dosing with 20 mg/kg of continuous one shot intravenous injection. 6. Urinary recovery rates during the first 8 hours (one is 6 hours, two is 9 hours) after 20 mg/kg intravenous bolus injection of CZX tended to be lower in 3 day-old or younger infants than in 5 day-old or older infants. 7. Eleven infants with various bacterial infections were given CZX by intravenous bolus injection or drip infusion. Dosage of CZX used in the present study were 36-148 mg/kg/day in 2-3 divided doses. Duration of treatment ranged from 3 to 12 days. Clinical efficacy of CZX was excellent or good in all the infants with acute bronchitis, acute pneumonia, suspected sepsis infected in uterine, acute otitis media, cellulitis, meningitis caused by Klebsiella pneumoniae and Escherichia coli, acute urinary tract infection and periproctic abscess except 1 case of acute bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation on ceftriaxone administered intravenously in neonates].

Ceftriaxone (CTRX) was clinically evaluated and its pharmacokinetics studied in neonates. The results obtained are summarized below. 1. Blood levels of CTRX at 8 to 12 hours after intravenous injection with a single dose of 10 to 20 mg/kg ranged from 14.9 to 32.8 micrograms/ml, while T1/2 ranged from 8.2 to 24.8 hours. 2. Blood levels of CTRX at 11 hours after the completion of drip infusion which lasted one hour with a dose level 10 to 20 mg/kg, ranged from 10.6 to 25.0 micrograms/ml, while T1/2 was 5.4 to 22.8 hours. 3. Multiple intravenous administrations were given to premature infants, but blood levels did not show evidence of drug accumulation. 4. Urinary excretion in 6 hours after an intravenous injection or a drip infusion with 10 approximately 20 mg/kg of CTRX ranged from 13.8 to 58.5% of the dosage. 5. The subjects in this study were 9 neonates with suspected sepsis, pneumonia, Staphylococcus epidermidis or Staphylococcus aureus infections (sepsis, staphylococcal scalded skin syndrome, pneumonia), acute bronchitis or meconium aspiration syndrome. Efficacies CTRX were excellent or good in all these cases administered in a daily dose of 19.5 to 41.6 mg/kg for 4 to 11 days. 6. No general side effects or abnormalities were observed in blood count, or hepatic or renal function.

[Pharmacokinetics and clinical effects of aspoxicillin in pediatric patients].

Since the efficacy and the safety of aspoxicillin (ASPC, TA-058) have been established on adult patients and the need of ASPC use on pediatric patients was anticipated, we performed a 16 center study on the clinical utility of ASPC in pediatric patients. 1. Pharmacokinetics ASPC was intravenously administered to 45 patients at a dose of 10, 20 or 40 mg/kg by one shot. Serum concentrations of ASPC were dependent of dose levels, and maximum levels of 58.4-230.8 micrograms/ml and half-lives (beta) of 1.08-1.16 hours were observed. Urinary recovery rates were 62.7-67.2% in 6 hours. Results obtained upon drip infusions (0.5-1 hour) were similar to one shot injections. 2. Clinical results (1) Clinical effectiveness Of 318 evaluable patients including 175 boys and 143 girls, 18.2% were nurslings and 61% were young children under 4 years of age. One hundred eighty six patients from whom causative organisms were isolated were classified as A group. Among them were 5 patients suffered with sepsis, but the ASPC treatment eradicated all the bacteria but Salmonella java in 1 case. All of 4 patients with meningitis were cured and all causative organisms (3 cases with Haemophilus influenzae and 1 case with Gram-positive coccus) were eradicated. Cure rates were 90% for 130 patients with respiratory tract infection, 88.6% for 35 with urinary tract infection, 85.7% for 7 with skin soft tissue infection and 89.8% for all the A group patients. Meanwhile, no causative organisms were isolated from 132 patients (B group patients) but cure rate of 91.7% was obtained for this group. No statistical difference was observed between A and B groups. For all the patients (318), the cure rate was 90.6%. (2) Bacteriological effects Of 63 Gram-positive bacteria isolated as pathogens, 58 strains were eradicated. Of 117 Gram-negative bacterial, 101 were eradicated. The eradication rate on all 180 strains was 88.3%. Overall, ASPC showed excellent effects against Streptococcus. Among strains of Staphylococcus aureus, 18 of 20 strains were eradicated. Of 59 strains of H. influenzae, 52 were eradicated and 3 decreased. Among strains of Escherichia coli, 25 of 28 strains were eradicated. Of Pseudomonas aeruginosa, 2 strains were decreased and one was unchanged. (3) ASPC was effective in 93.3% of 30 patients with serious infections and 79.2% of 72 patients with underlying diseases. Cure rates for patients with and without underlying disease were significantly different statistically (chi 2: P less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

[The study of flomoxef in the pediatric field].

Flomoxef (FMOX; 6315-S), a new synthetic oxacephem antibiotic, was studied in the pediatric field and pharmacokinetic and clinical results obtained were summarized below. 1. The activity of FMOX against Staphylococcus aureus isolated from clinical patients, including latamoxef resistant strains was very high and MIC was approximately less than or equal to 0.39 microgram/ml. This MIC value was lower than other cephem antibiotics such as cefotaxime, cefotiam, cefmetazole, cefamandole. The distribution of MIC's of FMOX against Escherichia coli and Salmonella spp. ranged from 0.05 to 0.78 microgram/ml and from 0.05 to 0.39 microgram/ml, respectively. 2. Serum concentrations of FMOX after dosages of 20 mg/kg and 40 mg/kg with 1 hour intravenous drip infusion were 21.5-27.5 micrograms/ml, 6.00-7.81 micrograms/ml, 0.37-0.59 micrograms/ml at 1, 2, 5 hours after administration, respectively, and T1/2(beta) were 0.61-0.83 hour. Serum concentrations after one shot intravenous injection of 20 mg/kg FMOX were 56.7-90.2 and 0.20-0.26 micrograms/ml at 3-10 minutes and 6 hours after administration, respectively, T1/2(beta) was 1.22 hours and urinary excretion rate was 66.7-69.8% in 6 hours. 3. FMOX was administered to 32 cases (upper and lower respiratory tract infection, and purulent infections) at 3-4 times daily for 4-13 days. In these cases the daily dosage amounted to 41-119 mg/kg. Clinical effectiveness was 97% overall including resistance cases upon other cephem antibiotic treatment. All bacterial species identified including Branhamella catarrhalis, Streptococcus pyogenes, S. aureus, Streptococcus agalactiae, and Haemophilus influenzae were eradicated upon the treatment with FMOX. 4. Only 3 cases of soft stool, 1 case of elevated GOT and GPT, and 1 case of elevated GPT were observed, and all of these adverse reactions were normalized after the completion of treatment.

[Studies on the intravenous administration of amikacin to neonates].

Amikacin (AMK) was administered mainly to neonates by either intravenous drip infusion or intramuscular injection and its pharmacokinetic changes were investigated. The results obtained are summarized as follows. 1. Serum half-lives of AMK in neonates at ages 0 to 3 days were longer than those at ages 4 to 10 days. Serum half-lives were prolonged particularly in neonates at an age 0 day. Neonates at ages 11 to 15 days, also showed longer half-lives in comparison to infants. Similar peak serum levels were observed in all the neonates with ages 0-15 days. 2. Similar serum AMK levels were obtained in neonates through intravenous drip infusion and through intramuscular injection at a same dose level. 3. When the drug was administered to neonates at 3.0 to 6.0 mg/kg by intravenous drip infusion, peak serum levels did not reach 30 micrograms/ml which is considered to be the critical level for AMK to be toxic. 4. Urinary excretion rates in neonates 11 day or older were almost the same levels as in infants. 5. AMK, when administered through intravenous drip infusion, was observed to have a higher migration rate to saliva when compared with kanamycin administered through intramuscular injection. 6. Based on the results obtained from the present study, the following doses seem to be optimal for neonates, but further studies are required to be conclusive. For neonates: 2.0 to 5.0 mg/kg daily in 1 to 2 divided doses. (For those at ages of 0 to 3 days: 2.0 to 3.0 mg/kg) For infants: 3.0 to 8.0 mg/kg daily in 1 to 2 divided doses through intravenous drip infusion over a period of 30 minutes to 1 hour.