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)     

Laboratory and clinical studies of ceftazidime in the pediatric field

The authors have carried out the laboratory and clinical studies of ceftazidime ( CAZ ) and obtained the following results. The antibacterial activities of CAZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, C. freundii and P. aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to CAZ ranged from 3.13 to 100 micrograms/ml, and the peak of distribution was 12.5 micrograms/ml. The peak of susceptibility distribution of E. coli, K. pneumoniae and E. cloacae was 0.2 micrograms/ml, and the distribution of E. aerogenes ranged from 0.1 to 100 micrograms/ml and that of S. marcescens, from 0.05 to 3.13 micrograms /ml. The growth of 92% of P. aeruginosa was inhibited at the concentration of 3.13 micrograms/ml or lower. For pharmacokinetic study, CAZ was given in a single dose of 10 mg/kg by intravenous administration for 5 minutes in 1 child and by drip infusion for 30 minutes in 2 children. After intravenous administration of CAZ , the serum level got to the peak of 41.0 micrograms/ml at 15 minutes, and was 1.0 micrograms /ml at 6 hours. Half-life time was 1.30 hours. With drip infusion of CAZ , the mean peak serum level was 52.45 +/- 2.05 micrograms/ml on completion of the infusion, and 1.05 +/- 0.05 micrograms/ml at 6 hours. Half-life time was 1.30 hours. CAZ was effective in 9 cases out of 11 cases with bacterial infection. No side effect was observed except for elevation of serum GOT and GPT in 1 case and eosinophilia in 1 case.     

Laboratory and clinical studies of T-1982 (cefbuperazone in pediatric field

The authors have carried out the laboratory and clinical studies of T-1982 (cefbuperazone). The results were as follows: The sensitivity was estimated by the plate dilution method on 28 strains of S. aureus 26 strains of E. coli, 27 strains of K. pneumoniae, 25 strains of S. marcescens and 14 strains of Proteus sp. isolated from patients. The distribution of susceptibility of S. aureus was 1.25-25 micrograms/ml and the peak of distribution was 12.5 micrograms/ml. The strains of 84.6% of E. coli were inhibited at concentration of less than 0.39 micrograms/ml. The strains of 77.8% of K. pneumoniae were inhibited at concentration of less than 0.2 microgram/ml. The strains of 96% of S. marcescens was inhibited at concentration of less than 3.13 micrograms/ml. The distribution of susceptibility of Proteus sp. was 0.39-25 micrograms/ml. T-1982 was given to intravenous administration for 5 minutes and drip infusion for 30 minutes a single dose of 20 mg/kg of T-1982 to 2 and 2 children respectively. After intravenous administration of T-1982, the mean serum level was peak 88.4 +/- 8.7 micrograms/ml at 15 minutes, 52.5 +/- 2.7 micrograms/ml at 1 hour, 4.6 +/- 0.15 micrograms/ml at 6 hours respectively. Half-life was 89 minutes. And after drip infusion of T-1982, the mean serum level was 75.5 +/- 3.5 micrograms/ml at 30 minutes and 3.1 +/- 0.6 micrograms/ml at 6.5 hours respectively. Half-life was 82 minutes. The mean urinary excretion rate was 94.7%, 57.4 +/- 11.0% up to 6 hours after intravenous administration and drip infusion respectively. T-1982 was effective in 13 cases out of 13 cases with bacterial infections. No side effects were observed except for 1 case with elevation of serum GOT, 1 case with elevation of serum GPT and 2 cases with eosinophilia.     

Experimental and clinical evaluation of cefsulodin in the pediatric field

Antimicrobial, pharmacokinetic and clinical evaluation of cefsulodin (CFS) was made and the following results were obtained. 1. Antimicrobial activity of CFS against P. aeruginosa was similar to a little lower than that of GM. Antimicrobial activity of CFS against S. aureus was similar to that of SBPC and against E. coli CFS showed lower antimicrobial activity. 2. Twenty or 50 mg/kg CFS was administered by 1 hour intravenous drip infusion. Average serum levels at the completion of the infusion were 35.1 +/- 8.0, 114.5 +/- 36.1 micrograms/ml and 1.6 +/- 0.7, 4.5 +/- 3.2 micrograms/ml at 6 hours afterward with the half life times of 1.50, 1.29 hours respectively. In case of 12.1 mg/kg 1 hour intravenous drip infusion, peak serum level was 13.4 micrograms/ml at the completion of infusion, and the concentration in the sputum was 1.0 micrograms/ml at 5 hours after completion of infusion. Average serum levels of CFS by one shot infusion of 20 mg/kg were 58.4 +/- 6.8 micrograms/ml, 2.7 +/- 2.5 micrograms/ml at 15 minutes and 6 hours after injection respectively. Half-life time was 1.54 hours. Average urinary excretion rates of CFS were 64.4%, 64.2% and 48.9% up to 6 hours after 1 hour intravenous drip infusion of 20 mg/kg, 50 mg/kg CFS and one shot intravenous of 20 mg/kg CFS respectively. 3. CFS was administered to 2 pneumonia cases caused by P. aeruginosa, i.e. one was 15 years and 11 months old male accompanying bronchial asthma and the another 4 years old male with LENNOX syndrome. Neither bacteriological nor clinical efficacy was, however, observed. Side effect as well as bacterial superinfection were not observed.     

Laboratory and clinical studies of cefuzonam in pediatric field

We have carried out laboratory and clinical studies of cefuzonam. The results were summarized as follows: The effectiveness of cefuzonam was estimated by a plate dilution method on 26 strains each of S. aureus, E. coli, K. pneumoniae, Salmonella spp. and P. aeruginosa and 27 strains of S. marcescens isolated from patients. The distribution of MIC's of cefuzonam against S. aureus was 0.39 approximately 1.56 micrograms/ml and the peak of the distribution was 0.39 microgram/ml. Strains of 96.2% of E. coli and Salmonella spp. were inhibited at cefuzonam concentrations less than 0.39 microgram/ml. Strains of 92.3% of K. pneumoniae were inhibited at drug concentrations less than 0.20 microgram/ml. The distribution of MIC's of cefuzonam against S. marcescens was less than or equal to 0.025 approximately 12.5 micrograms/ml and the peak of the distribution was 0.2 microgram/ml and 1.56 microgram/ml. MIC's against P. aeruginosa was 12.5 approximately greater than 100 micrograms/ml. Cefuzonam was given by 5-minute intravenous administration to 4 children and 1-hour drip infusion to 1 child at a single dose of 20 mg/kg. After the intravenous administration, mean serum levels of cefuzonam were 30.8 +/- 4.55 microgram/ml at 30 minutes, 13.8 +/- 1.83 micrograms/ml at 1 hour, 0.4 +/- 0.159 microgram/ml at 6 hours. The half-life was 1.12 +/- 0.198 hours. After the drip infusion, the serum levels of the drug were 38.7 micrograms/ml at 1 hour, 5.25 micrograms/ml at 2 hours and 0.087 microgram/ml at 7 hours. The half-life was 0.93 hour. The mean urinary excretion rate was 58.1% and 33.4% up to 6 hours after the intravenous administration and the drip infusion, respectively. Cefuzoname was effective in 4 out of 5 cases with bacterial infections. No side effect due to the drug was observed in any case.     

Experimental and clinical studies on ceftizoxime in the field of oral surgery (author's transl)

Experimental and clinical studies on ceftizoxime (CZX), a new cephalosporin derivative, were carried out and the following results were obtained. 1. The minimal inhibitory concentrations of CZX, cefazolin (CEZ), cephalothin (CET), cefotiam (CTM) and cefmetazole (CMZ) against Gram-positive cocci (31 strains) and Gram-negative rods (169 strains) isolated from the patients with oral infections were determined. CZX, though somewhat less active against Gram-positive cocci than the other cephalosporins, was the most active of the antibiotics tested against Gram-negative rods. 2. The mean serum levels in 19 patients who received 1 g of CZX by intravenous drip infusion for 1 hour were as follows. 19.6 micrograms/ml 30 minutes after the start of intravenous drip infusion, 52.2 micrograms/ml after 1 hour, 25.0 micrograms/ml after 1.5 hours, 20.3 micrograms/ml after 2 hours, 7.9 micrograms/ml after 4 hours, 3.5 micrograms/ml after 6 hours. The mean peak tissue levels of CZX after 1 g dose by intravenous drip infusion for 1 hour were 14.3 micrograms/g (n = 5) in gingiva and 8.5 micrograms/g (n = 2) in bone marrow at the end of intravenous drip infusion. 3. CZX was administered to 17 patients with various infections in the oral surgical field at daily dose of 1 approximately 2 g for 3 approximately 6 days. The therapeutic effect was as follows: 'excellent' in 6 cases, 'good' in 9, 'fair' in 1 and 'poor' in 1. The final rate of effectiveness was 88.2%. No adverse reaction was observed except for 2 cases of slight elevation of S-GPT.     

Fundamental and clinical studies on imipenem/cilastatin sodium in the pediatric field

Fundamental and clinical studies were performed on a newly developed carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), and results were summarized as follows. The antibacterial activity of MK-0787 at an inoculum of 10(6) cells/ml against strains of S. aureus which were sensitive or resistant to cefazolin (CEZ), E. coli, P. mirabilis, K. pneumoniae, S. marcescens and P. aeruginosa were determined and compared with activities of ceftazidime (CAZ), CEZ, cefmetazole (CMZ), ceftizoxime (CZX), latamoxef (LMOX), cefamandole (CMD), cefoperazone (CPZ), cefsulodin (CFS) and piperacillin (PIPC). The peak MIC of MK-0787 was less than or equal to 0.024 micrograms/ml against S. aureus, which were sensitive or resistant to CEZ, 0.10 micrograms/ml against E. coli, P. mirabilis, or K. pneumoniae, 0.39 micrograms/ml against S. marcescens and 1.56 micrograms/ml against P. aeruginosa. The antibacterial activity of MK-0787 against these bacteria was, on the whole, superior to that of CAZ, CEZ, CMZ, CZX, LMOX, CMD, CPZ, CFS or PIPC. The pharmacokinetics of MK-0787/MK-0791 was studied in 10 children at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg by a 30-minute intravenous drip infusion. Maximum serum levels of MK-0787, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg were 41.6 micrograms/ml and 72.9 micrograms/ml, respectively, at the end of infusion and 0.1 micrograms/ml at 6 hours, respectively, after drip infusion. The half-life of both dose levels was 0.9 hour. Mean peak serum levels of MK-0791, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 49.7 micrograms/ml and 87.0 micrograms/ml, respectively, with half-life of 1.1 and 0.6 hour, respectively. Urinary recovery rates of MK-0787 for 6 hours at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 47.8-82.7% and 25.5-78.0%, respectively, and of MK-0791 for 6 hours were 51.7-93.4% and 40.3-94.4%, respectively. Twenty-four patients, including 1 with purulent meningitis, 1 with septicemia, 1 with pyothorax, 10 with bronchopneumonia, 7 with pyelonephritis and 4 with infections of cutaneous soft tissue were treated with MK-0787/MK-0791 at dose levels of over 100 mg/100 mg/kg/day with purulent meningitis and septicemia and 28.8 mg/28.8 mg-72.8 mg/72.8 mg/kg/day with other infections. The clinical response in all patients was excellent or good.(ABSTRACT TRUNCATED AT 400 WORDS)     

Laboratory and clinical studies of flomoxef in the pediatric field

We have carried out laboratory and clinical studies on flomoxef (FMOX, 6315-S). The results were summarized as follows. FMOX was given by 5-minute intravenous administration to 3 children at a single dose of 20 mg/kg. After the intravenous administration, mean serum levels of FMOX were 110.1 +/- 30.95 micrograms/ml at the end of injection, 44.4 +/- 10.55 micrograms/ml at 15 minutes, 11.0 +/- 1.72 micrograms/ml at 1 hour and 0.42 +/- 0.17 microgram/ml at 6 hours. The mean half-life was 1.14 +/- 0.30 hours. The mean urinary excretion rate was 68.8 +/- 17.4% up to 6 hours after the intravenous administration. FMOX was given by 30-minute drip infusion to 2 children at a single dose of 20 mg/kg and to 3 children at a single dose of 40 mg/kg. After the 30-minute drip infusion, mean peak serum levels of FMOX obtained for the 2 dose levels were 45.5 +/- 0.45 micrograms/ml and 87.4 +/- 18.35 micrograms/ml at the end of injection, respectively, and mean half-lives were 0.63 +/- 0.23 hours and 0.70 +/- 0.27 hours, respectively. The mean urinary excretion rate was 53.4 +/- 6.1% up to 6 hours after the 30-minute drip infusion of 40 mg/kg FMOX. Treatment with FMOX was made in 24 cases of pediatric bacterial infections; 5 cases of purulent tonsillitis, 2 cases of bronchopneumonia, 12 cases of pneumonia, and 1 case each of lymphadenitis, pyothorax, purulent meningitis, cellulitis, and abscess. Results obtained were excellent in 15 cases and good in 9 cases. No significant side effect due to the drug was observed in any cases.     

Fundamental and clinical evaluation on ceftriaxone in the pediatric field

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies on the pharmacokinetics of cefotaxime in neonates

The pharmacokinetics of cefotaxime was investigated in neonates. The following results were obtained. 1. The peak serum concentration of cefotaxime, seen 15-minutes after a single intravenous of 20 mg/kg, was 51.6 +/- 9.3 mcg/ml by bioassay. After 6 hours the mean serum concentration decreased to 5.6 +/- 3.1 mcg/ml. Concentrations obtained by HPLC paralleled those determined by bioassay. The peak serum concentration of the desacetyl metabolite was attained 30 minutes to 2 hours after injection. The mean serum desacetyl metabolite concentration was about 1/2.5 times higher than the cefotaxime concentration. The half-life was inversely related to the age of the neonates, decreasing to 1.64 hours on day 11 postpartum. 2. Serum concentrations determined by bioassay and HPLC after administering a dose of 10 mg/kg of cefotaxime by 30-minute intravenous drip infusion were comparable. The peak serum concentration at the completion of intravenous drip infusion was 21.0 mcg/ml by bioassay. The half-life of cefotaxime was 2.85 hours. The peak serum concentration of the desacetyl metabolite, seen at the completion of intravenous drip infusion, was about 1/2 times that of the peak cefotaxime concentration. 3. The peak serum concentration at the completion of a 30-minute intravenous drip infusion of 20 mg/kg displayed a mean value of 33.5 +/- 10.3 mcg/ml by bioassay. After 6 hours the mean serum concentration was 4.0 +/- 1.0 mcg/ml. The peak serum concentration of the desacetyl metabolite, seen at the completion of infusion to 2 hours thereafter, was equivalent to about 1/2.2 the peak cefotaxime concentration. 4. Mean urinary excretion rate of cefotaxime in 2-day-old neonates was 23.4% by bioassay 6 hours after a 30-minute intravenous drip infusion of 10 mg/kg. The mean urinary excretion rate of the desacetyl metabolite was 8.7%. Mean 6-hour excretion rates in 2-day-old and 4-day-old neonates administered 20 mg/kg of cefotaxime by 30-minute intravenous drip infusion were 6.2% and mean 37.7%, respectively. The corresponding values for the desacetyl metabolite were 2.4% and 12.4%, respectively.     

Pharmacokinetic and clinical studies on amikacin in neonates

Pharmacokinetic and clinical studies on amikacin (AMK) were performed in neonates and the results obtained are summarized as follows. 1. After intramuscular injection of single doses of AMK at 3 mg/kg, peak serum levels were 6.8 micrograms/ml in a 2-day-old neonate and 7.0 micrograms/ml in a 20-day-old neonate. Serum levels of AMK in the above 2 neonates at 8 hours after injection were 1.5 micrograms/ml and 1.4 micrograms/ml, respectively, and the half-life of AMK was 3.3 hours. After intramuscular injection of single doses of 4 mg/kg of AMK, the mean peak serum level was 8.1 +/- 1.1 micrograms/ml, and half-lives of AMK were 6.1 hours in a 1-day-old neonate and 4.0 hours in a 3-day-old neonate. The mean peak serum level of AMK reached at 1 hour after intramuscular administrations at single dose of 6 mg/kg was 10.5 +/- 0.5 micrograms/ml in a 3-day and a 4-day-old neonates. Serum levels at 8 hours after administrations were 3.1 micrograms/ml and 2.8 micrograms/ml, in the 3-day and the 4-day-old neonates, respectively. Half-lives of AMK in sera were 3.9 hours in the 3-day-old neonate and 3.5 hours in the 4-day-old neonate. 2. In three 2-day-old neonates, the mean peak serum level of AMK after an intravenous drip infusion for 30 minutes at single dose of 3 mg/kg was 10.0 +/- 1.1 micrograms/ml at the end of infusion and serum levels decreased to 2.3 +/- 0.6 micrograms/ml at 6.5 hours after infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laboratory and clinical studies on cefuroxime (author's transl)]

The authors have carried out the laboratory and clinical studies of cefuroxime (CXM). The results were as follows: The sensitivity was measured by plate dilution method on 26 strains of S. aureus, 22 strains of E. coli and 24 strains of K. pneumoniae isolated from patients. The distribution of sensitivity of S. aureus was 0.78 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 1.56 approximately 50 micrograms/ml and the peak was 6.25 micrograms/ml. The growth of 79.2% K. pneumoniae was inhibited in concentration of less than 3.13 micrograms/ml. CXM was given intravenously for 30 minutes at a single dose of 20 mg/kg to 3 children. The serum mean levels of CXM were 99.0 +/- 10.6 micrograms/ml at 30 minutes, 18.0 +/- 10.7 micrograms/ml at 1 hour, 7.0 +/- 2.0, 2.2 +/- 0.6, 0.79 +/- 0.2 microgram/ml at 2, 4 and 6 hours after drip infusion for 30 minutes, respectively. Mean half life was 48 minutes. The mean urinary recovery rate was 96.2% up to 8 hours after administration. CXM was effective in 9 of 10 cases of bacterial infections. No side effect was observed except for 1 case with elevation of serum transaminase.     

Laboratory and clinical studies on cefamandole (author's transl)]

The authors have carried out the laboratory and clinical studies of cefamandole (CMD). The results are as follows: The sensitivity was measured by plate dilution method on 26 strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and 14 strains of Salmonella typhimurium isolated from patients. The distribution of sensitivity of S. aureus was 0.39 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 0.78 approximately greater than 100 micrograms/ml, and K. pneumoniae, 1.56 approximately greater than 100 micrograms/ml. The distribution of sensitivity of Salmonella typhimurium was 6.25 approximately greater than 100 micrograms/ml and its peak was 6.25 micrograms/ml. CMD were given intravenously for 30 and 60 minutes at a single dose of 25 mg/kg body weight to 6 children. The serum mean levels of CMD were 105.3 micrograms/ml at 30 minutes, 15.1 micrograms/ml at 1.5 hours, 1.6 micrograms/ml at 2.5 hours after drip infusion for 30 minutes, respectively, and 34.7, 5.2, 0.6 micrograms/ml at 1, 2, 3 hours after drip infusion for 60 minutes, respectively. And the serum level at 4 hours after administration was not detected. The mean urinary excretion rates were 73.3% in the drip infusion for 30 minutes and 60.7% in its for 60 minutes, up to 8 hours after administration. Half life was 26 minutes. CMD was effective in 18 of 21 cases of bacterial infections. No side effects were observed except for 2 cases with elevation of serum transaminase.     

Laboratory and clinical studies of sulbactam/ampicillin in pediatric field

We have carried out laboratory and clinical studies on sulbactam/ampicillin (SBT/ABPC). The results are summarized as follows. SBT/ABPC was given by 30-minute drip infusion to 1 child at a single dose of 15 mg/kg and to 2 children at a single dose of 30 mg/kg. After the 30-minute drip infusion, peak serum levels of ABPC(SBT) obtained for the 2 dose levels were 18.0 micrograms/ml (12.4 micrograms/ml) for the former dose level and 81.0 micrograms/ml (53.7 micrograms/ml) and 300 micrograms/ml (200 micrograms/ml) for the latter at the end of injection, and half-lives were 0.84 hour (0.82 hour) for the former and 0.96 hour (1.44 hours) and 0.93 hour (1.19 hours) for the latter. In another trial, SBT/ABPC was given to 1 child at a single dose of 60 mg/kg. After the 30-minute drip infusion, peak serum level of ABPC (SBT) was 82.3 micrograms/ml (45.9 micrograms/ml), and half-life was 1.20 hours (1.36 hours). The urinary excretion rates of ABPC (SBT) were 51.3% (49.5%), 55.8 +/- 10.4% (65.3 +/- 9.1%), 74.0% (76.1%) up to 6 hours after the 30-minute drip infusion of 15 mg/kg, 30 mg/kg and 60 mg/kg, respectively. Treatment with SBT/ABPC was made in 21 cases of pediatric bacterial infections: 8 cases of tonsillitis, 4 cases of bronchitis, 3 cases of pneumonia and 1 case each of pharyngitis, peritonsillar abscess, lymphadenitis, impetigo, abscess and urinary tract infection. Results obtained were excellent in 14 cases, good in 7 cases. No significant side effect due to the drug was observed in any cases except 1 case of fever and rash.     

Studies on panipenem/betamipron in the field of pediatrics]

Pharmacokinetic and clinical studies in pediatrics were performed on panipenem/betamipron (PAPM/BP), a combined drug of a carbapenem antibiotic (panipenem) and organic ion inhibitor (betamipron) at a weight ratio of 1:1. 1. Plasma levels and urinary excretion were studied when PAPM/BP, at 10 mg/10 mg/kg (4 cases) or 20 mg/20 mg/kg (5 cases), was administered using intravenous drip infusion in 30 minutes to 9 children (4-14 years old). The plasma PAPM level at the end of drip infusion was 30.75 +/- 4.98 micrograms/ml in the cases administered with 10 mg/10 mg/kg and 68.72 +/- 5.73 micrograms/ml in the cases administered with 20 mg/20 mg/kg. Drug concentrations then gradually decreased with half-lives of 1.08 +/- 0.09 hours and 0.98 +/- 0.02 hour, and reached 0.39 +/- 0.14 micrograms/ml and 0.62 +/- 0.06 micrograms/ml, respectively, after 5.5 hours. Plasma BP levels at the end of drip infusion was 18.93 +/- 3.75 micrograms/ml in the cases administered 10 mg/10 mg/kg and 37.09 +/- 2.68 micrograms/ml in the cases administered 20 mg/kg, and half-lives were 0.55 +/- 0.07 hour and 0.61 +/- 0.03 hour, respectively; the plasma BP level could not be determined in any cases after 5.5 hours. Mean urinary recovery rates of PAPM in the first 6 hours after the start of intravenous drip infusion were 33.0 +/- 6.1% in the cases administered 10 mg/10 mg/kg and 21.8 +/- 2.3% in the cases administered 20 mg/20 mg/kg and those of BP were 77.0 +/- 2.4% and 76.6 +/- 7.3%, respectively. 2. When PAPM/BP, was administered at 31.3 mg/31.3 mg/kg thought by intravenous drip infusion in 30 minutes to 1 case of purulent meningitis, PAPM levels were 0.76 micrograms/ml at the end of drip infusion but varied between 0.80 to 1.97 micrograms/ml 30 minutes after the end of drip infusion during 8 days of treatment. 3. PAPM/BP was administered to 43 cases, 47 diseases of bacterial infections in the domain of pediatrics to study its clinical efficacy, bacteriological efficacy and adverse reactions. Single doses were 5.2mg/5.2mg to 31.3 mg/31.3 mg/kg; frequencies of administration were 3 to 4 times a day, and durations of administration were 3 1/3 to 11 days; and total dosages ranged between 1.125 g/1.125 g and 11.0 g/11.0 g.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies of meropenem in pediatric infections]

Pharmacokinetic and clinical evaluations of meropenem (SM-7338, MEPM) were carried out in pediatric patients. The following results were obtained. 1. After 30-minute intravenous drip infusion at a dose of 20 mg/kg, plasma concentrations of MEPM reached their peaks at the end of drip infusion with an average value of 48.8 +/- 3.64 micrograms/ml, and the average plasma half-life was 0.93 +/- 0.21 hour in the beta-phase. After 30-minute intravenous drip infusion at a dose of 10 mg/kg, the average peak plasma concentration was 27.7 +/- 4.33 micrograms/ml and the average plasma half-life was 0.78 +/- 0.20 hour. 2. Urinary excretion rates of MEPM after 30-minute intravenous drip infusion at doses of 20 and 10 mg/kg were 44.8 +/- 4.54% and 40.9 +/- 1.78%, respectively. 3. MEPM was administered to 13 cases (upper and lower respiratory infections, pneumonia and lymphadenitis) at daily doses between 60-90 mg/kg/day divided into 3 dosages using 30-minute intravenous drip infusion. Clinical responses were "excellent" in 12 patients, "good" in 1, hence an efficacy rate of 100% was obtained. 4. Bacteria identified in various disease cases included 12 strains of 5 species, and the eradication rate was 100%. 5. No side effects were observed in any children. Laboratory test results showed abnormalities in 2 cases with elevations of GOT and GPT. These results suggest that MEPM may be a very useful and safe drug for the treatment of pediatric infections.     

Pharmacokinetic and clinical studies of cefotiam in mature neonates

Pharmacokinetic and clinical studies on cefotiam (CTM) in mature neonates were carried out. The results were summarized as follows: The serum peak level of CTM after intravenous bolus injection at a single dose of 10 mg/kg was found at 15 minutes after the injection. The serum peak level was 32.9 micrograms/ml in a 1 day-old neonate and it was 17.7 micrograms/ml in a 4 day-old neonate. Serum levels at 6 hours after injection were 4.5 micrograms/ml and 0.7 microgram/ml for the 1 day-old and the 4 day-old, respectively. Half-lives were 2.1 and 1.2 hours in the 1 and 4 day-old neonates, respectively. Serum peak levels of CTM at 15 minutes after intravenous bolus injection at a single dose of 20 mg/kg were 40.9 micrograms/ml in a 1 day-old neonate and 36.5 micrograms/ml in a 5 day-old neonate. Serum levels of CTM at 6 hours were 8.0 micrograms/ml in the 1 day-old neonate and 2.3 micrograms/ml in the 5 day-old neonate. Half-lives were 2.5 and 1.5 hours in the 1 and 5 day-old neonates, respectively. With each dosage, the younger showed extended half-lives. A dose-response relationship was observed. In 2 cases of 2 day-old neonates given CTM 20 mg/kg by 30-minute intravenous drip infusion, the mean peak concentration at the termination of the infusion was 25.1 micrograms/ml. Even after 6 hours the concentration was found at 8.7 micrograms/ml. Half-lives were 2.9 and 3.7 hours. Urinary excretion rates of CTM in 1 to 5 day-old neonates were as low as about 20% in any of cases subjected to a 10 mg/kg intravenous bolus injection, a 20 mg/kg intravenous bolus injection a 20 mg/kg 30-minute intravenous drip infusion. It was possible to evaluate the efficacy of CTM in only 1 case of pneumonia. CTM was clinically and bacteriologically effective in this case. No abnormal clinical symptoms and findings were observed in all of the 5 cases.     

Investigation on the use of amikacin in the newborn

The use of amikacin (AMK) in newborns was investigated and the results obtained are summarized as follows. 1. AMK was administered to 3 rabbits at an intramuscular dose of 6 mg/kg. Mean blood levels determined according to methods of bioassay (BIO) and fluorescent immunoassay (FIA) were 28.6 and 22.2 micrograms/ml, respectively, at 30 minutes after dosing. Then, the blood levels declined rapidly. Mean T 1/2 values obtained with the above 2 assay methods were 0.76 and 0.63 hours, respectively. 2. When AMK was administered at a dose of 5.7 mg/kg to a 64 day-old newborn by drip intravenous infusion for 30 minutes, a peak blood level was attained at the end of drip intravenous infusion, which was 20.0 micrograms/ml according to BIO and was 15.5 micrograms/ml according to FIA. The blood levels declined gradually thereafter with a T 1/2 value of 2.33 hours (BIO) or 2.03 hours (FIA). When the drug was administered at 5.3 mg/kg to a 26 day-old newborn using the same infusion method, the peak blood level obtained at the end of drip intravenous infusion was 18.0 micrograms/ml according to BIO and was 14.8 micrograms/ml according to FIA, and T 1/2 values were 4.76 and 3.68 hours, respectively. 3. As there was a close correlation between the values obtained with BIO and with FIA in both rabbits and clinical cases, with a coefficient of 0.990, and also the BIO values could be estimated using a formula of FIA value X 1.2 + 2.2, it would be possible to monitor AMK levels in the blood of patients at bedside using the FIA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical studies on the effect of imipenem/cilastatin sodium on infections in obstetrics and gynecology. Tissue concentrations and clinical effects

Tissue transfer and clinical effects of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic, were studied and the following results were obtained. Penetrations of MK-0787 into uterine arterial blood and into pelvic dead space exudate were good. When MK-0787/MK-0791 was administered at a dose of 500 mg/500 mg by a 30-minute intravenous drip infusion, the peak level of MK-0787 in uterine arterial blood was 22.2 micrograms/ml, 30 minutes after the completion of the drip infusion. The peak level of MK-0787 in pelvic dead space exudate was 12.9 micrograms/ml at 2 hours and it dropped to 2.6 micrograms/ml at 6 hours. MK-0791 levels were similar to those of MK-0787. Penetrations of MK-0787 into tissues were also good. When MK-0787/MK-0791 was administered at a dose of 500 mg/500 mg by a 30-minute intravenous drip infusion, the level of MK-0787 was 2.2 +/- 1.1 micrograms/g in the oviduct, 2.7 +/- 2.1 micrograms/g in the ovary, 2.5 +/- 1.2 micrograms/g in the endometrium, 3.0 +/- 1.6 micrograms/g in the myometrium, 3.1 +/- 1.9 micrograms/g in the cervix uteri and 3.8 +/- 2.0 micrograms/g in the portio vaginalis at 1 hour after administration. These levels were reduced to halves, respectively, in approximately 2 hours. Four patients with intrauterine infections and 2 with vaginal stump infections were treated with MK-0787/MK-0791 at a daily dose of 1 g/1 g (500 mg/500 mg X 2). Good clinical and bacteriological responses were observed in 5 patients and causative organisms were eradicated in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic study of cefsulodin in children

Cefsulodin (CFS), a cephem antibiotic, was administered to 26 children aged from 11 months to 11 years by intravenous injection or intravenous 1-hour drip infusion in doses of 15 and 50 mg/kg body weight to investigate serum and urinary concentrations. The following results were obtained. Serum concentration The serum concentrations of CFS at 5 minutes after intravenous injection of 15 and 50 mg/kg were 57.1 and 224.2 micrograms/ml, respectively. The biological half-lives (T 1/2 beta) were 1.28 and 1.12 hours. The serum concentration of CFS after intravenous 1-hour drip infusion reached a peak at the end of infusion, i.e. 29.9 micrograms/ml for 15 mg/kg and 121.9 micrograms/ml for 50 mg/kg, and T 1/2 beta were 1.22 hours for 15 mg/kg and 1.27 hours for 50 mg/kg. The AUC was proportional to the doses for both intravenous injection and intravenous drip infusion. The serum clearance was about twice the value in adults and the distribution volume was about 1.5 times as large. Urinary excretion The urinary excretion up to 6 hours after administration was: 69.0% for 15 mg/kg and 61.9% for 50 mg/kg in cases of intravenous injection, and 62.4% for 15 mg/kg and 71.1% for 50 mg/kg in cases of intravenous 1-hour drip infusion. The percent urinary excretion was similar to that in adults.