Dry syrup and tablet of newly developed cefpodoxime proxetil (CS-807, CPDX-PR) was investigated in the departments of pediatrics of 17 institutes and their related hospitals.
1. Pharmacokinetics of CPDX-PR in pediatrics were investigated. Peak blood levels of CPDX at dose levels of 3 mg/kg and 6 mg/kg were 2. 24± 0. 21 and 4. 68± 0. 54 μ g/ml, respectively, in fasting and 1. 65± 0. 07 and 3. 71± 0. 41μ g/ml, respectively, after meal. Urinary recovery rates in 6 hours were 31. 2± 2. 2% of dose in average.
2. Clinical efficacies of CPDX-PR on various infectious diseases were studied in 748 cases. Clinical efficacy rate in 499 cases with causative bacteria isolated was 94. 6%: efficacy rates for individual infections were 96. 8% (120/124) for tonsillitis, 96. 0% (96/100) for urinary tract infection, 93. 5% (58/62) for pneumonia, 92. 4% (61/66) for impetigo, 100% (32/32) for scarler fever and 93. 2% for pharyngitis or laryngitis. Bacteriological eradication rate for Gram-positive organisms was 91. % (244/268); and for Gram-negative organisms, 89. 7% (210/234). The clinical efficacy rate for cases which were non-responsive to previous antibiotic therapy was 88. 1% (74/84).
3. Side effects and clinical laboratory findings were investigated in 779 cases. Two each of vomiting, loose stool and rash, 10 of diarrhea and 1 of diarrhea associated with candidiasis were reported, but no serious side effects were noted. There was no serious laboratory test abnormality except slight elevations of eosinophile, platelet, transaminase or prolongation of prothrombin time, totalling 34 occurrences.

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Twenty nine children were treated with cefpodoxime proxetil (CPDX-PR, CS-807) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 2 months to 10 years. Dose levels of CPDX-PR ranged from 7. 5 to 12. 0 mg/kg/day for 5 to 12. 7 days. The 29 patients included 9 tonsillitis, 2 otitis media, 5 scarlet fever, 3 bronchopneumonia, 1 lymphadenitis, 8 urinary tract infections and 1 staphylococcal scalded skin syndrome, and they were evaluated for the clinical efficacy of CPDX-PR. Results were excellent in 21 and good in 8 patients. Out of the 29 patients, 3 cases showed diarrhea and 2 cases showed elevated GOT and GPT.
The pharmacokinetics of CPDX-PR was studied in 9 patients whose ages ranged from 1 to 9 years. The serum peak concentrations of CPDX in 5 patients were between 1. 37 and 4. 10 μ g/ml (mean: 2. 53 μ g/ml) at 1 to 6 hours after dosing 3 mg/kg before meals. Those of 4 patients ranged 3. 29 to 4. 88 μ g/ml (mean: 4. 36 μ g/ml) at 2 hours after administering 6 mg/kg before meals. Portions of CPDX excreted into urine within 6 hours ranged from 20. 3 to 34. 3% (mean 27. 1%) in 5 patients who were given 3 mg/kg, and ranged from 24. 1 to 65. 7% (mean 41. 1%) in 4 patients given 6 mg/kg.

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Clinical studies on cefpodoxime proxetil (CS-807, CPDX-PR) dry syrup were carried out in the field of pediatrics, and the results are summarized as follows.
1. Eleven year-old male and 12 year-old female were administered orally at a dose level of 5. 6 and 6. 0 mg/kg, respectively, after or before meal. C_max and T 1/2 were 5. 0 μ g/ml and 2. 13 hours, respectively, for the male and 4. 04 μ g/ml and 1. 63 hours, respectively, for the female.
2. Good clinical responses were obtained in 21 of 22 child patients with bacterial pharyngitis, tonsillitis, scarlet fever and urinary tract infections. One child with Mycoplasma pneumonia did not respond.
As to bacteriological effects, eradication of pathogens was observed in 8 out of 11 strains, showing an eradication rate of 72. 7%.
3. As to side effect, 1 case of loose stool was observed, but there was no need of discontinuing the drug treatment.

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Cefpodoxime proxetil (CPDX-PR, CS-807) was given orally to 18 children with acute bacterial infections including 10 with acute tonsillitis, 3 with acute bronchitis, 1 with pneumonia, 3 with staphylococcal scalded skin syndrome and 1 with infectious impetigo.
Daily dosages per kg bodyweight ranging from 7. 5 to 18 mg were given in 2 or 3 divided doses per day for 5 to 15 days.
Clinical responses were excellent in 3 (16. 7%), good in 11 (61. 1%), fair in 4 (22. 2%) and poor in 0 (0%), with an overall efficacy rate of 77. 8%.
Good bacteriological responses were obtained in 6 out of the 7 cases from which pathogens were identified. No side effect was observed.
The above results suggest that CPDX-PR is a useful new oral cephalosporin derivative for the treatment of bacterial infections in children.

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Clinical studies of cefpodoxime proxetil (CPDX-PR), a new cephem antibiotic, were carried out in 60 patients in the pediatric field.
The overall efficacy rate on 54 patients with various infections was 98. 1%, and few side effects, all of them very mild, were developed in 6 of 60 patients (10%). It was concluded that CPDX-PR was one of the most useful antibiotics in the pediatric field because of the high efficacy rate and the safety.

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Children with acute infections were treated with cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephalosporin.
1. A girl of 4 years old, weighing 17kg, and another girl of 12 years old, weighing 33kg, were administered orally each 3mg/kg of CPDX-PR. Blood levels of CPDX reached peaks of 1.39 and 2.26μg/ml at 4 hours-post-dose, and T 1/2 were 2.09 and 2.63 hours, respectively. Cumulative urinary recovery rates for 8 hours were 57.3 and 80.9%, respectively.
2. A total of 30 patients was treated with CPDX-PR. These patients included 10 with acute tonsillitis, 6 with acute bronchitis, 5 with bronchopneumonia, 2 with scarlet fever and 2 with urinary tract infections, and one each with acute pneumonia, acute otitis media, acute otitis media plus sweat gland abscess, staphylococcal scalded skin syndrom and acute lymphadenitis. The treatment was effective in 27 cases out of 29 (except one with an unknown response) with a clinical efficacy rate of 93.1%.
3. Bacteriological responses to CPDX-PR were as follows; eradication of pathogen in 7, and unknown in 2 out of 9 cases from whom pathogens had been isolated prior to the treatment.
4. As a side effect, diarrhea was observed in 1 patient, but it was possible to continue the treatment. With regard to laboratory tests, a slight elevation of GOT and slight elevations of GOT and GPT were found in 1 case each.

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Cefpodoxime proxetil (CS-807, CPDX-PR), a new cephalosporin antibiotic, was investigated for its usefulness in pediatrics.
1. The total number of patients treated were 21 with their ages ranging from 3 months to 9 years and 1 month, consisting of 5 male and 16 female infants.
2. Single dosages of the drug ranged between 4.4mg and 5.8mg/kg with oral administration for 3 times daily in fasting. A total aggregated dosage was between 46.4mg/kg and 200.0mg/kg. The length of administration was 3 to 12 days.
3. The breakdown of symptoms were 9 cases of acute pharyngitis, 5 cases of acute tonsillitis, 3 cases of acute bronchitis, and 1 case each of impetigo +purulent rhinitis, cervical lymphadenitis, scarlet fever, and urinary tract infection.
4. The clinical efficacy rate was 100% with 18 excellent responses and 3 good responses.
5. The bacteriological efficacy rate was 90.9% in eradication rate, based on results on 17 strains of suspected causative microorganism among which 10 strains were eradicated, 1 strain was decreased, and 6 strains were unknown.
6. There was no side effect during the treatment and after the discontinuation, while, in clinical laboratory tests, GOT and GPT were elevated in 1 case which was judged as abnormal. No patient refused the drug.
CPDX-PR was considered to be very useful drug because of its excellent efficacy and safety in pediatrics in treating infectious diseases.

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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 3.0mg/kg and 4.4mg/kg of CPDX-PR were 1.26-1.46μg/ml and 1.45μg/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 6mg/kg were 97.5%, and that at a single dose of 1mg/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 6mg/kg and 1mg/kg were 91.3% and 9.5%, 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.

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In bacteriological, pharmacokinetic and clinical studies of cefpodoxime proxetil (CPDX-PR, CS-807), the following results were obtained:
1. Antibacteriological activity
Antibacteriological activity of R-3746 (Na-salt of cefpodoxime), cefaclor (CCL), caphalexin, cefroxadine (CXD), cefazolin (CEZ), cephalothin (CET) and amoxicillin (AMPC) were studied against clinical isolated bacteria following as: Staphylococcus aureus (resistant or sensitive of methicillin), Escherichia coli (resistant or sensitive to CEZ), Klebsiella pneumoniae (resistant or sensitive to CEZ), Proteus mirabilis and Enterobacter cloacae. Antibacterial activities of CXD and CET, however, were not tested against methicillin resistant S. aureus (MRSA) or CEZ resistant E. coli and K. pneumoniae. R-3746 showed stronger activities than any of the other oral antibiotics against these strains except S. aureus against which it showed slightly less activity than AMPC. Most frequent MIC values of R-3746 to S. aureus, E. coli, K. pneumoniae and P. mirabilis were 1.56, 0.39, ≤0.10 and ≤0.10μg/ml, respectively. Against isolated strains of MRSA, MICs of R-3746 were higher than 25μg/ml with 23 strains (77%), which were similar to MIC values of CCL and AMPC against these organisms. MIC values of R-3746 against CEZ resistant E. coli and K. pneumoniae were superior to MICs of other antibiotics, and the MIC₅₀ value was 0.20μg/ml. Against many isolated strains of E. cloacae MIC values of R-3746 were relatively high ranging 0.78 to 100μg/ml. MIC₅₀ of R-3746 against E. cloacae was 12.5μg/ml.
2. Absorption and excretion
Serum concentration and urinary excretion of CPDX (the active form of CPDX-PR) were studied upon single oral administration of CPDX-PR at 3mg/kg, 6mg/kg (dry syrup) or 100mg (tablet). The peak of serum concentration of CPDX was attained in 1-6 hours 1-4 hours and 2-6 hours after administration of CPDX-PR at the 3 different dosage levels, and they were 0.99-2.99μg/ml, 4.30-7.05μg/ml and 1.65-2.93μg/ml, respectively. At 8 hours after administration, mean concetrations of CPDX for the 3 groups were 0.31, 0.83 and 0.66μg/ml, respectively. As the average AUC's for the 3 groups were 8.16, 25.97 and 10.79μg·hr/ml, respectively. Urinary recovery rates of CPDX for the 3 groups were 20.9-56.2, 28.3-49.7 and 35.1-50.4%, respectively in the first 8 hours after administration.
3. Clinical study
CPDX-PR was given orally to 60 cases consisting of 2 cases of pharyngitis, 19 cases of tonsillitis, 2 cases of bronchitis, 6 cases of scarlet fever, 12 cases of pneumonia, 9 cases of skin and soft tissue infections, 9 cases of urinary tract infections and 1 case of acute otitis media. Clinical evaluation in 54 cases resulted in 90% effectiveness. Bacteriological effect was evaluated against 42 strains of causative organisms. Forty strains were eradicated or decreased and the efficacy rate was 95.2%. No adverse reaction or abnormal laboratory test values were observed in any of the cases.

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Pharmacokinetic, bacteriological and clinical studies on cefpodoxime proxetil (CPDX-PR, CS-807), a newly developed oral cephem, were carried out in the treatment of infectious diseases in the field of pediatrics.
1. Since CPDX demonstrates very powerful antimicrobial actions against such Gram-negative bacilli as Escherichia coli, Salmonella sp., Klebsiella pneumoniae and Serratia sp., such Gram-positive cocci as Streptococcus pyogenes and Streptococcus pneumoniae, and β-lactamase producing Branhamella catarrhalis and Haemophilus influenzae, this drug was thought to be useful for the treatment of pediatric infectious diseases when main causative bacteria in the field of pediatrics were taken into account.
2. When changes in blood and urine concentrations of CPDX following the administration of this drug at 3.7mg/kg before meal were determined, C_max and T 1/2 were found to be 2.98μg/ml at 2-hour and 1.73 hours, respectively; an urinary excretion rate in the first 6 hours and a maximum urine concentration were 32.5% and 52μg/ml, respectively.
3. Clinically, 8 of 8 patients with the upper respiratory tract infections (100%), 28 of 29 patients with bronchitis and/or pneumonia (96.6%), 3 of 4 patients with otitis media (75%), 2 of 2 patients with sinusitis (100%), 3 of 3 patients with the skin soft tissue infections (100%), 1 of 1 patient with bacterial enteritis (100%) and 11 of 14 patients with urinary tract infections (78.6%) responded well to the treatment with CPDX-PR, showing a 91.8% efficacy rate in all the patients treated.
4. Bacteriologically, Staphylococcus aureus, Staphylococcus epidermidis, S. pyogenes, S. pneumoniae, E. faecalis, B. catarrhalis, H. influenzae, E. coli and Salmonella typhimurium were all eradicated from 5, 1, 4, 6, 1, 5, 5, 11 and 1 patient, respectively. An eradication rate in all the patients examined was 97.5% (39/40).
5. Gastrointestinal symptoms appeared as side effects in 2 of 71 patients (vomiting in 1 and diarrhea in 1), hence, an incidence of side effects was 2.8% (2/71). As for abnormal laboratory findings, eosinophilia, thrombocytosis and increases in GOT and GPT were observed in 3 of 39 patients examined (7.7%), 1 of 39 patients (2.6%) and 2 of 34 patients (5.9%), respectively.
In addition, we also examined the effect of the drug on the hemostatic system, but found no changes upon the treatment.
Based on these results, it appeared that CPDX-PR was a useful and safe drug in treatment of infectious diseases in the field of pediatrics when administered 2-3 times a day at a dose of 3-6mg/kg.

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Cefpodoxime proxetil (CPDX-PR, CS-807) was evaluated for its efficacy, safety and pharmacokinetics in children. CPDX-PR was effective in 93.6% of 47 cases with respiratory tract, middle ear, skin or urinary tract infections. Twice or 3 times daily administration of 3mg/kg each was sufficient to treat streptococcal pharyngitis and Haemophilus influenzae infections.
No severe adverse reaction was encountered in 52 cases treated with CPDX-PR. The serum half-life was approximately 2.17±0.24 hours after oral administration.

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Pharmacokinetic, bacteriological, and clinical studies in pediatrics on cefpodoxime proxetil (CPDX-PR, CS-807)(pediatric dry syrup) were performed.
1. Serum concentrations and urinary excretions of CPDX after administration of CPDX-PR to children (ages between 6 and 14) were investigated.
Four cases were administered with CPDX-PR at a dose level of 3mg/kg 30 minutes before or after meal. Effects of timings of administration were investigated using a crossover study. Average serum concentrations in the group administered with the drug before meal reached their peaks at 1 hour after administration with an average level of 2.34±0.16μg/ml and diminished with a half-life of 1.94±0.08 hours to 0.29±0.04μg/ml at 8 hours after administration. In the group administered with the drug after meal, average serum concentrations attained their peaks at 4 hours after administration at an average level of 1.93±0.09μg/ml, and decreased with a half-life of 2.08±0.19 hours to 0.58±0.16μg/ml at 8 hours.
Urinary recovery rates of CPDX in the first 8 hours after administration of CPDX-PR in the before-meal and the after-meal groups averaged 34.4±6.3% and 38.5±7.0%, respectively.
In a separate experiment, 7 cases were administered with CPDX-PR, 30 minutes after meal, at a dose level of either 3 or 6mg/kg. Effects of the 2 different dose levels were investigated also using a crossover study. Average serum concentrations at their peaks attained at a 4 hours after administration for the 2 dosage groups (3 and 6mg/kg) were 1.76±0.11 and 3.08±0.41μg/ml, respectively. Average half-life values for the 2 groups were 2.40±0.14 and 2.25±0.07 hours, respectively, with average 8 hour values of 0.64±0.10 and 1.30±0.21μg/ml, respectively. Urinary recovery rates in the first 8 hours after administration averaged 40.4±3.2% and 46.3±6.5%, respectively. From these results, it appeared that the absorption of the drug was affected by the timing of administration (before or after meal), and the presence of ingested foods in the digestive system delayed the absorption. The overall quantity absorbed, however, did not seem to be affected by the timing of administration. These data also showed that serum and urinary concentrations of the drug depended on dose levels.
2. CPDX-PR was administered to 61 pediatric patients (their ages ranged between 4 months and 10 years and 2 months) with various infections, and clinical and bacteriological effects and adverse reactions were investigated. Clinical effects were evaluable in 58 cases including 6 cases of acute pharyngitis, 10 cases of acute purulent tonsillitis, 4 cases of acute bronchitis, 18 cases of acute pneumonia, 9 cases of acute urinary tract infection, 5 cases of impetigo, 1 case of furunculosis, 2 cases of acute purulent lymphadenitis, and 3 cases of acute purulent otitis media. Clinical responses were excellent in 41 cases, effective in 15 cases, fairly effective in 1 case and failure in another with an efficacy rate of 96.6%.
Antimicrobial effects against a total of 33 strains identified or assumed to be pathogenic bacteria were evaluated. The 33 strains of bacteria included 6 strains of Staphylococcus aureus, 1 strain of Staphylococcus epidermidis, 6 strains of Streptococcus pyogenes, 1 strain of Streptococcus pneumoniae, 1 strain of Enterococcus faecalis, 8 strains of Escherichia coli, 10 strains of Haemophilus influenzae. All the bacteria listed here were judged to have been eradicated except each one strain of S. aureus and H. influenzae, thus, the eradication rate was 93.9%.
No adverse side reactions were observed.

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Bacteriological, pharmacokinetic and clinical studies on cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows.
1. Antibacterial activities of R-3746 (Na-salt of cefpodoxime (CPDX)) against clinically isolated strains of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Enterococcus faecalis, Branhamella catarrhalis, Escherichia coli, Proteus mirabilis and Haemophilus influenzae were compared with those of cefaclor, cephalexin and cefadroxil. R-3746 is superior to other antibiotics against S. pneumoniae, S. pyogenes, B. catarrhalis and Gram-negative rods.
2. Serum concentrations of CPDX after administration of CPDX-PR at doses of 3mg/kg (fasting), 6mg/kg (non-fasting) and 6mg/kg (fasting) were determined. Mean AUC (area under curve)'s of CPDX obtained were 9.60, 31.35 and 17.89μg·hr/ml, respectively for the 3 dosages. The mean half-lives of CPDX were 3.35, 1.88 and 1.76 hours, respectively. The mean urinary recovery rate within 8 hours after administration of CPDX-PR at a dose of 3mg/kg (fasting) was 39.2%.
3. CPDX-PR was administered to 37 pediatric patients with various bacterial infections (pyelonephritis 9, cystitis 4, pneumonia 7, acute bronchitis 3, otitis media 2, tonsillitis 10, subcutaneous abscess 1 and purulent lymphadenitis 1). The overall clinical efficacy rate was 91.9% and the overall bacteriological eradication rate was also 91.9%.
4. No adverse reactions were observed. Abnormal laboratory findings were moderate, eosinophilia in 2 and slight elevation of GOT and GPT in 1. The taste and the odor of the CPDX-PR preparation was sufficiently tolerable.
From the above results we have concluded that CPDX-PR is a useful oral antibiotic in the treatment of bacterial infections in children.

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We have carried out laboratory and clinical studies on cefpodoxime proxetil (CS-807, CPDX-PR).
The results are summarized as follows.
CPDX-PR was given via oral administration to each 2 children at a single dose of 3mg/kg and to each of 3 children in a 100mg tablet. After the oral administration, mean peak serum levels of CPDX obtained for the 2 dose levels were 1.86±0.35μg/ml and 2.16±0.63μg/ml at 2 hours, respectively, and mean half-lives were 1.31±0.02 hours and 1.47±0.18 hours, respectively.
The mean urinary excretion rate of CPDX was 32.8±1.0% in the first 12 hours after the oral administration of 3mg/kg. When a dose of 100mg tablet was given to each of the 3 children, urinary excretion rates in the first 12 hours were 43.5%, 48.6% and 24.8%, respectively.
Treatment with CPDX-PR was done in 38 cases of pediatric bacterial infections; 19 cases of tonsillitis, 3 cases of pharyngitis, 1 case of bronchitis, 3 cases of pneumonia, 3 cases of scarlet fever, 2 cases of impetigo, 4 cases of UTI and 1 case each of phlegmone, subcutaneous abscess and balanitis. Results obtained were excellent in 23 cases, good in 15 cases.
No significant side effect due to the drug was observed in any cases.

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Cefpodoxime proxetil (CPDX-PR, CS-807) dry syrup was administered orally to 31 patients with various infections at daily dose levels between 5.4 and 10.9mg/kg divided into three doses.
1. The subjects were 3 patients with urinary tract infections, 25 with tonsillitis and 1 patient each with bronchitis, pneumonia, and cervical lymphadenitis. Clinical effects were excellent in 16 cases, good in 14, and fair in 1 (tonsillitis), with an overall efficacy rate of 96.8%.
2. Organisms suspected as pathogens were 32 strains (6 strains of Staphylococcus aureus, 2 of Streptococcus pyogenes, 1 of Enterococcus faecalis, 15 of Haemophilus influenzae, 5 of Haemophilus parainfluenzae and 3 of Escherichia coli). Bacteriologically, eradication of pathogens were observed in 30 strains, decrease in one (H. parainfluenzae), and no change in another (E. faecalis), thus the eradication rate was 93.8%.
3. Side effect was observed in 1 case (slight eruption) but it was possible continue the treatment. Abnormal laboratory test values were observed in 1 case each of a slight prolongation of prothrombin time and eosinophilia, but they were not serious. Diarrhea was not observed in any patients.
4. All the medication was done on schedule. No refusal of the drug occurred due to its taste or odor.

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Cefpodoxime proxetil (CPDX-PR, CS-807) is a new oral cephem derivative drug in which carboxylic acid was esterified to the 4-position of CPDX (oxime type cephem antibiotic). CPDX-PR is hydrolyzed mainly with esterase in intestinal wall and CPDX exists as an active form in body fluid. While there are numerous study reports using CPDX-PR in tablet forms in Japan, the dry syrup formula for pediatric use was newly developed.
The dry syrup of CPDX-PR was orally administered 20 minutes after meal to the 6 boys of ages from 8 years and 1 month to 10 years and 10 months, with doses of 3 and 6 mg/kg, respectively, for 3 cases each. Serum concentrations and urinary concentrations and recovery rate of the drug were investigated.
In addition to the above, the clinical and bacteriological studies were performed in a total of 105 cases consisting of children with ages ranging from 2 months to 11 years and 8 months, upon administering an average dose of 3.4 mg/kg, 3 to 4 times per day (96 cases of 3 times and 9 cases of 4 times). The 105 cases included 13 cases of pharyngitis, 21 cases of tonsillitis, 4 cases of acute bronchitis, 6 cases of pneumonia, 1 case of pleurisy, 13 cases of scarlet fever, 41 cases of urinary tract infection, 3 cases of posthitis and 3 cases of bacillary dysentery.
Drug sensitivity test was performed for the following strains:(i) Strains retained by our department; 52 strains of Streptococcus pyogenes, 18 strains of Streptococcus agalactiae, and 11 strains of Bordetella pertussis, and (ii) strains isolated from cases to which CPDX-PR was administered; 2 strains of Staphylococcus aureus, 8 strains of S. pyogenes, 2 strains of Haemophilus influenzae, 10 strains of Escherichia coli, and 1 strain of Proteus mirabilis.
Drug sensitivities of the strains retained by our department were tested with the inoculum sizes of 10⁸ and 10⁶ cfu/ml for R-3746 (Na-salt of CPDX), cefaclor (CCL), cephalexin (CEX), amoxicillin (AMPC), and methicillin (DMPPC), and those against strains separated from the cases to which CPDX-PR was administered were tested with the same inoculum sizes for R-3746, CCL, CEX, cefadroxil, ampicillin (ABPC), DMPPC and cloxacillin (MCIPC).
Adverse reactions and abnormal clinical laboratory test results were also examined. The results obtained are summarized as follows.
1. In both of the dosage level groups of 3 and 6 mg/kg, average serum concentrations of CPDX reached their peaks at 2 hours after administrations and the peak levels of the 2 groups were 2.00 and 4.27 μg/ml, respectively. Thus, a dose response was observed. The average half-life times for the 2 groups were very close to each other, and were 2.03 and 2.28 hours, respectively.
Average AUC values for the 2 groups were 10.65 and 21.80 μg·hr/ml, respectively, and the dose response was observed here, also.
2. Urinary concentrations of CPDX in the same cases were measured, and they attained peaks in 2 to 4 hours after administration of 3 mg/kg, and in 4 to 6 hours after dosing of 6 mg/kg, with average peak levels of 171.3 and 265 μg/ml, respectively. Average urinary recovery rates after 8 hours were similar in the 2 dose level groups with values of 44.7 and 43.5%, respectively.
3. Clinical responses were evaluated in 103 cases out of 105 cases, and 100 cases were rated as good or excellent with an efficacy rate of 97.1%.
4. Bacteriological effects of CPDX-PR were determined for 46 strains. The results were excellent with the disappearance of 42 strains and a disappearance rate of 91.3%.
5. MIC₉₀'s of R-3746 to 52 strains of S. pyogenes with inoculum sizes of 10⁸ and 10⁶ cfu/ml among the strains retained by our department were 0.05 and 0.0128 μg/ml, respectively. These values are similar to MIC's of AMPC, and smaller than MIC's of other 3 drugs tested.

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The influence of cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients.
CPDX-PR dry syrup was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of bacteria: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No notable changes were observed in fecal viable cell counts except that slight decreases of E. coli counts were observed on the days 3 to 5 after starting administration.The subjects in the pediatric study were 5 children with infections, 3 boys and 2 girls at ages from 1 year 1 month to 6 years 10 months, with their body weights ranging from 9.3 to 23.8 kg. CPDX-PR dry syrup was administered at a dose between 3.0 to 3.7 mg/kg, 3 times a day for 4 to 7 days. Although some variations of the fecal bacterial flora were noticed between subjects during the administration of CPDX-PR, no notable changes were observed in major aerobic and anaerobic bacteria such as Enterobacteriaceae, Enterococcus, Bacteroides and Bifidobacterium in 4 of the 5 cases. Large decreases in Streptococcus, Enterobacteriaceae, Bifidobacterium, Eubacteriurn and anaerobic cocci and an increase in Enterococcus were observed in the other case. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. Regarding Enterobacteriaceae, transitory bacterial replacement was observed within the genus.
Fecal concentration of CPDX during the administration of CPDX-PR was extremely low or below the detectable limit except one specimen from a case in which intestinal bacterial flora showed remarkable changes.
From the above, CPDX-PR appears to be a drug with a relatively small influence on the intestinal bacterial flora.

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Concurrently with administering a newly developed cephem derivative antibiotic (CEP), cefpodoxime proxetil (CPDX-PR, CS-807) dry syrup, to children with skin and soft tissue infections, activities of 7 drugs against a group of microorganisms were tested. The drugs tested included 4 drugs of the cephem group, R-3746, a Na-salt form of CPDX, cefaclor (CCL), cephalexin (CEX) and cefadroxil (CDX), and 3 drugs of the penicillin group, ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC). The bacterial strains tested were 71 strains of Staphylococcus aureus and 1 strain of Streptococcus pyogenes, all isolated from the above cases of pediatric infections. Inoculum sizes used in these tests were 10⁶ and 10⁸ cfu/ml.
Ages of children in those cases to which the drug was administered ranged from 2 months to 15 years. A total of 66 cases were treated, including 60 cases of impetigo, 5 cases of subcutaneous abscess and 1 case of phlegmon. The drug was administered for an average of 6 days with a daily average dose level of 9.4 mg/kg divided into 3 doses except 1 case where a twice daily dose regimen was used.
Clinical and bacteriological effects were examined, and the occurrence of adverse reactions and abnormal laboratory test results were recorded. The results of these tests are summarized below.
1. The activity test for R-3746 (Na-salt of CPDX) against 71 strains of S. aureus performed at an inoculum level of 10⁸ cfu/ml showed 2 peaks of MIC values, one in a range of 1.56 to 6.25 μg/ml and the other higher than 100 μg/ml.
The most prevalent MIC value was 3.13 μg/ml with MIC against 51 strains or 71.8% of the strains tested showing this value, and MIC values of 25 μg/ml or higher were obtained for 13 strains or 18.3% of the strains tested.
The MIC₈₀ was 6.25 μg/ml. Thus, R-3746 showed an antibacterial activity slightly weaker than MCIPC and DMPPC but similar to CCL, CEX and CDX.
MIC values obtained at an inoculum level of 10⁶ cfu/ml also had 2 peaks, one in a range of 1.56 to 3.13 μg/ml and the other higher than 25 μg/ml. Strains against which R-3746 had the MIC value of 3.13 μg/ml were the most numerous with 47 strains or 66.2%, and strains against which the MIC value of higher than 25 μg/ml was obtained were next with 13 strains or 18.3%.
The MIC₈₀ with 10⁶ cfu, ml was 3.13 μg/ml, very close to the MIC₈₀ obtained at the inoculum size of 10⁸ cfu/ml. The antibacterial activity of R-3746 determined at 10⁶ cfu/ml was in agreement with that determined at 10⁸ cfu/ml, and slightly weaker than MCIPC, ABPC and DMPPC, but similar to CCL, CEX and CDX.
2. MICs of R-3746 against the tested strain of S. pyogenes at inoculum levels of 10⁸ and 10⁶ cfu's/ml were both lower than 0.05 μg/ml. Thus, the antibiotic activity of R-3746 against this strain of S. pyogenes was similar to ABPC and MCIPC, and superior to those of CCL, CEX, CDX and DMPPC.
3. Clinical effects of CPDX-PR in the 66 cases mentioned above were judged by doctors in charge. Efficacy ratios obtained were as follows: 93.3% for the 60 cases of impetigo and 100% for all the other cases including 1 case of phlegmon and 5 cases of subcutaneous abscess. Hence the total efficacy rate was excellent, 93.9%. The 60 cases of impetigo were classified into 3 dose level groups: less than 4.9 mg/kg, between 5.0 and 9.9 mg/kg, and higher than 10 mg/kg. Clinical effects were evaluable in the latter 2 groups with efficacy rates of 92.7% and 100%, respectively.
4. Clinical effects determined through scores were evaluable in 62 cases 3 days after starting administration and the efficacy rate obtained was 71.0%.

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