Pharmacokinetic and clinical studies on flomoxef in the pediatric field

The new antibiotic flomoxef (FMOX, 6315-S) was administered to 38 children. The results obtained are summarized as follows. 1. In 3 cases of children administered with FMOX (20 mg/kg) by intravenous drip infusion for 30 minutes, the mean T1/2 (beta) was 0.96 hour and the mean 6-hour urinary excretion was 95.5%. 2. The antibiotic was administered to a total of 38 patients with bronchopneumonia, lacunar tonsillitis, upper respiratory tract infection complicated with brain tumor, otitis media, urinary tract infection, purulent meningitis, subcutaneous and hyponychial abscess, cervical lymphadenitis, or bacterial enteritis. The treatment was markedly effective in 24 cases, effective in 13, fair in 1, and ineffective in none. The efficacy rate was 97.4%. From our results, this drug appears to be particularly effective to bronchopneumonia, upper respiratory tract infection and urinary tract infection. 3. None of the children showed clinical symptoms indicating side effects of the drug. These results showed that FMOX is a drug that can be safely used in the pediatric field as well as for adults.     

Pharmacokinetic and clinical studies on cefuzonam in the pediatric field

A multi-center open study was conducted to investigate cefuzonam (L-105, CZON), a newly developed cephalosporin from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows. Serum concentrations and urinary excretion. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg, via one shot intravenous injection or intravenous drip infusion over 1 hour. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after one shot intravenous injections were: 52.8 micrograms/ml with the dosage of 10 mg/kg, 135 micrograms/ml with 20 mg/kg, and 317 micrograms/ml with 40 mg/kg, and T1/2 beta's for the 3 dosages were 1.07 hours, 0.91 hour, and 1.01 hours, respectively. With 1-hour intravenous drip infusion, mean serum concentrations at the end of infusion were: 22.4 micrograms/ml with 10 mg/kg, 46.3 micrograms/ml with 20 mg/kg, 72.5 micrograms/ml with 40 mg/kg, and 69.2 micrograms/ml with 50 mg/kg, and T1/2 beta's for these dosages were 1.31 hours, 1.45 hours, 0.84 hour, and 0.66 hour, respectively. In 6 hours after administration of CZON, urinary excretion rates were 43.5-51.4% for one shot intravenous injections of 10-40 mg/kg, and 42.7-58.6% for 10-50 mg/kg drip infusions. Concentrations in cerebrospinal fluid Penetrations into cerebrospinal fluids in patients with purulent meningitis achieved levels of 2.80-6.40 micrograms/ml with the administration of CZON at 100 mg/kg in acute cases of within 6 days after onset. When the administration of the drug was done at the earlier stage, the greater penetration occurred. However, rates of penetration were 3.10% to 5.03% within 4 days after a drug administration, thus, the penetration was not thought to be as good as other beta-lactam agents which achieve higher penetration rates. Clinical results Of 407 cases treated with CZON, 18 cases were excluded from the statistical analysis. The remaining 389 cases plus 8 cases each of which had 2 complicated diseases, with a total of 397, were statistically analyzed for the clinical effectiveness of this drug against various infections. The efficacy was evaluated as "good" or "excellent" in 248 out of 266 cases from which pathogens were isolated, for an efficacy rate of 93.2%. The efficacy rate was 88.5% for 131 cases for which pathogens were unidentified, thus no statistically significant difference was noted between the 2 groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of clarithromycin in the pediatric field

Pharmacokinetic and clinical studies on clarithromycin (TE-031, A-56268), a new macrolide antibiotic, were performed in the pediatric field. 1. Pharmacokinetic investigation We studied serum concentrations and urinary excretions after single oral administration of TE-031 granules and tablets. Doses were 1, 5, 10 and 15 mg/kg body weight in case of granules (10% TE-031) and 150 mg/kg body weight in case of tablets (50 mg TE-031, 3 tablets). As results, Tmax's were 1-2 hours after administration in case of both granules and tablets. Cmax's in cases of granules were 0.29 +/- 0.15 micrograms/ml in 1 mg/kg administration, 2.53 +/- 0.71 micrograms/ml in 5 mg/kg, 4.11 +/- 1.37 micrograms/ml in 10 mg/kg, 6.28 +/- 1.48 micrograms/ml in 15 mg/kg showing a dose dependency. T 1/2's were 1.8-6.5 hours in cases of 1, 5, 10, 15 mg/kg of granules and tablets. T 1/2's became longer with increased doses. Urinary recoveries were 9.4 +/- 2.4% to 31.6 +/- 19.0% in 6 hours after administration. 2. Clinical investigation Clinical study was carried out in 24 patients of respiratory infections. Clinical efficacies were excellent in 11 patients, good in 12 patients and fair in 1 patient. The clinical efficacy rate was 95.8%. No side effects were observed. The above results suggest that TE-031 is a useful oral antibiotic for treating pediatric respiratory infections, especially those due to Mycoplasma pneumoniae.     

Pharmacokinetic and clinical studies of cefuzoname in the pediatric field

Newly developed cefuzoname (CZON) was tested in 21 children and serum and urinary concentration and urinary recovery rates were determined. To 9 cases, 3 groups of 3 cases each, CZON was given at 10, 20 or 40 mg/kg one shot intravenously, and to 12 cases, 3 groups of 5, 3, 4 cases each, 10, 20 or 40 mg/kg was drip-infused over 1 hour. To 1 case of purulent meningitis 55.6 mg/kg was given one shot intravenously and concentrations in cerebrospinal fluid (CSF) and serum were measured. In 37 pediatric patients comprising 1 with tonsillitis, 24 with pneumonia, 1 with purulent meningitis and bacteremia, 7 with urinary tract infection, and 1 each with staphylococcal scalded skin syndrome, purulent lymphadenitis, periarthritis of jaw joint, maxillary sinusitis and orbital abscess, CZON was tried at 21.6 mg/kg (mean) per dose, 3 or 4 doses daily, one shot intravenously, for 7 days (mean). The clinical efficacy and antibacterial effectiveness were investigated. Also, the side effects were investigated and clinical laboratory tests done in the 37 pediatric cases plus 6 cases in which CZON was used but which were excluded from the efficacy analysis because they did not involve infections. The following is a summary of the results: 1. To 3 groups of 3 children each, 10, 20 or 40 mg/kg of CZON was given one shot intravenously. In each case the maximum serum concentration was observed at 5 min. after injection, and mean values of 3 groups with 10, 20 and 40 mg/kg dosing were 57.1, 147.2 and 316.7 mcg/ml respectively, indicating a dose-dependent response among the 3 groups. Mean half-lives were 0.83, 1.10 and 0.79 hours for 10, 20 and 40 mg/kg groups, respectively. The 10 mg/kg and the 40 mg/kg groups showed similar half-lives but the half-life of the 20 mg/kg group was a little longer than those of the other 2. 2. CZON was drip-infused over 1 hour to a total of 12 children divided into 3 groups of 5, 3 and 4 children at dose levels of 10, 20 and 40 mg/kg, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of cefdinir in pediatric field

Cefdinir (CFDN) was evaluated for its efficacy and safety. The following results were obtained. 1. Pharmacokinetic study: CFDN was evaluated pharmacokinetically in 4 male children aged 9 to 13. CFDN was given orally to 3 children at a dose of 3 mg/kg. Peak plasma levels of 0.71 microgram/ml, 0.78 microgram/ml and 0.45 microgram/ml were attained in the 3 children, respectively, at 4 hours after dosing. Half-lives of CFDN in serum were 1.78 hours, 1.48 hours and 2.23 hours, respectively. The 12-hour urinary recovery rates of CFDN were 17.4%, 28.1% and 6.2%. When CFDN was given orally to the remaining child at a dose of 6 mg/kg, the peak plasma level was attained at 4 hours after dosing with a level of 1.16 micrograms/ml. T 1/2 was 1.78 hours. The 12-hour urinary recovery rate of CFDN was 15.0%. 2. Clinical study: CFDN 5 percent fine granules were given to 26 patients with infections; 2 with pneumonia, 4 with acute bronchitis, 1 with chronic bronchitis, 12 with pharyngitis, 4 with scarlet fever, 1 with otitis media and 2 with skin and soft tissue infections. Therapeutic responses were "excellent" in 15, "good" in 8, "fair" in 1 and "poor" in 2, with an efficacy rate of 88.5%. 3. Adverse reactions: As for adverse reactions, diarrhea was noted in 1 patient. It was concluded that CFDN is a useful drug for the treatment of the bacterial infections in pediatrics.     

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.     

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)     

Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field

Pharmacokinetic and clinical studies of sulbactam/ampicillin (SBT/ABPC) were conducted and the obtained results are summarized as follows. For pharmacokinetic investigation, SBT/ABPC at 30 or 60 mg/kg was administered by intravenous drip infusion over 30 minutes. The maximum blood concentration was reached just after the completion of the drip infusion in both groups. The mean peak serum concentrations of SBT and ABPC were 22.4 +/- 0.8 micrograms/ml and 32.8 +/- 1.0 micrograms/ml, respectively, in the 30 mg/kg group, and they were 54.2 micrograms/ml and 93.8 micrograms/ml, respectively, in the 60 mg/kg group. The concentrations were dose-related. The mean half-lives of SBT and ABPC following 30 mg/kg SBT/ABPC administration were 0.91 +/- 0.04 hour and 0.90 +/- 0.05 hour, respectively, and those following 60 mg/kg SBT/ABPC were 1.08 hours and 0.84 hour, respectively. The highest urinary concentration occurred 0-2 hours after the 30 minutes drip infusion. Mean urinary excretion rate of SBT and ABPC over 6 hours were 71.4 +/- 2.5% and 54.6 +/- 3.3%, respectively, in the 30 mg/kg group, and they were 80.0% and 63.7%, respectively, in the 60 mg/kg group. In the clinical investigation conducted with a total of 24 patients (15 with respiratory tract infections, 3 with urinary tract infections, 2 with lymphadenitis, and others), SBT/ABPC was found to be excellent in 14 cases, good in 9, fair in 1. The efficacy rate was, therefore, 95.8%. In the bacteriological evaluation, 9 out of 11 clinically isolated strains were eradicated, 1 unchanged and 1 unknown. The elimination rate was 90.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, a slight elevation of GOT was observed.     

Pharmacokinetic and clinical studies on cefprozil granules in the pediatric field]

Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-positive cocci (GPC) including 2 strains of Staphylococcus aureus, 49 strains of Streptococcus pyogenes, 4 strains of Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of Haemophilus influenzae, 18 strains of Escherichia coli, and 1 strain of Proteus mirabilis. MIC determination of these strains was done with an inoculum size of 10(6) CFU/ml. In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC). CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months. Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively. In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months. A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t.i.d. and 30 cases of q.i.d.) was administered for an average of 7 days. The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis. Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy. The results obtained are summarized as follows: 1. With regard to GPC, MICs of CFPZ against 2 strains of S. aureus were 0.78 or 1.56 micrograms/ml and CFPZ showed the second highest activity to MCIPC. MICs of CFPZ against 49 strains of S. pyogenes were all less than 0.025 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of sultamicillin granule in the pediatric field

Sultamicillin (SBTPC) is a combined drug of ampicillin (ABPC) and sulbactam (SBT) which is an inhibitor of beta-lactamase, in a clinical form of tosylate with equivalent molecules in ester linkages. A tablet form of this combined drug has been released since July, 1987 in Japan and now a granular form for pediatric patients has been developed. Hence, the granular form of SBTPC was administered to 6 boys (age: 8 years 5 months-11 years 5 months) to determine plasma and urinary concentrations of the drug and its urinary recovery-rates. The dose of 10 mg/kg or 15 mg/kg was given orally just after meal to 3 boys. To study clinical and bacteriological effects of this drug, a mean daily dose of 27.1 mg/kg divided 2-4 times a day was administered for 9 days on the average to a total of 57 cases with pharyngitis (5), tonsillitis (5), laryngitis (1), bronchitis (1), pneumonia (8), scarlet fever (1), typhoid fever (1), impetigo (16), furuncle (2), abscess (6), lymphadenitis (1) and urinary tract infection (10) except 2 cases which were unevaluable for clinical effects. MICs of 7 drugs (SBTPC, ABPC, SBT, methicillin (DMPPC), cloxacillin (MCIPC), cephalexin and cefaclor) against 12 of 22 strains isolated from patients with infections of skin and soft tissue were determined with inoculum-sizes of 10(8) and 10(8) CFU/ml to study beta-lactamase producing activities. Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients including dropped-out cases. The results obtained are summarized as follows. 1. Mean plasma peak levels of ABPC and SBT were observed at 1 hour after administration in both of the 10 mg/kg and the 15 mg/kg groups with values of 2.34 and 5.57 micrograms/ml for ABPC and 1.87 and 4.66 micrograms/ml for SBT, respectively. Mean concentrations of SBT were lower than those of ABPC in both groups and individuals. Dose-responses in plasma levels and AUCs were observed in both groups. Mean half-life values of ABPC and SBT in the 2 groups were 1.93 and 1.12 hours for ABPC and 1.97 and 1.22 for SBT, respectively. Mean half-life values for ABPC and SBT were similar in each group and this tendency was also seen among individuals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of cefpirome in pediatric field]

We conducted a study on the pharmacokinetics and clinical application of cefpirome (CPR) in children. 1. A single intravenous injection of 20 mg/kg of CPR was given to a two-month-old boy, and the concentration of the drug in the blood was measured. Fifteen minutes after administration, the concentration was 53.3 micrograms/ml, and it gradually decreased thereafter, reaching a level of 5.18 micrograms/ml after 8 hours with a half-life in the plasma of 2.36 hours. 2. A single intravenous injection of 700 mg (50 mg/kg) of CPR and that of cefotaxime (CTX) were given to a girl with suppurative meningitis (3 years old, 14 kg, causative bacteria, Haemophilus influenzae), and concentrations of the drugs in plasma and cerebrospinal fluid after 1 hour were measured. On the second day of illness, the concentration of CTX in the plasma was 39.4 micrograms/ml and the concentration of desacetyl-CTX (D-CTX) was 25.2 micrograms/ml, while concentrations in the cerebrospinal fluid were 6.22 micrograms/ml (15.8%) for CTX and 3.94 micrograms/ml (15.6%) for D-CTX. On the third day of illness, concentration of CPR in the plasma was 59.3 micrograms/ml, while its concentration in the cerebrospinal fluid was 7.44 micrograms/ml (12.5%). 3. CPR was intravenously administered in daily dosages of 37.7-75.0 mg/kg in 2-3 portions for periods of 4-15 days to 2 patients with septicemia (causative bacteria, Klebsiella pneumoniae in 1 case and Escherichia coli in the other), 1 patient with bronchitis (K. pneumoniae), 9 patients with pneumonia (1 case of Staphylococcus aureus, 3 cases of H. influenzae, 2 cases of Haemophilus parainfluenzae, 1 case of K. pneumoniae + Pseudomonas cepacia, 2 cases of H. influenzae + Branhamella catarrhalis), 2 patients with cellulitis (1 case of S. aureus, 1 case, causative agent unknown), 1 patient with suppurative lymphadenitis (causative agent, unknown), 1 patient with staphylococcal scalded skin syndrome, 1 patient with renal abscess (causative agent, unknown), and 1 patient with a urinary tract infection (E. coli), for a total of 18 patients, with excellent results in 9 cases and good results in 9 cases, hence an efficacy rate of 100% was obtained. 4. As an accompanying side-effect, eruption was observed in 1 of the 18 patients, but when administration was discontinued, the symptom gradually receded, and it disappeared by the 4th day.(ABSTRACT TRUNCATED AT 400 WORDS)     

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

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

Pharmacokinetic and clinical studies of cefteram pivoxil granule in the pediatric field

Cefteram pivoxil (CFTM-PI), the pivaloyloxymethyl ester of cefteram (CFTM) in which aminothiazol was also introduced into the 7 position of cephem nucleus, is a new oral cephem antibiotic. CFTM-PI was absorbed through the intestines and hydrolyzed to CFTM by esterases in the intestinal wall and existed in the body fluids as CFTM. A tablet form of this drug has been released in Japan and now a granular form for pediatric patients has been developed. We have determined MICs of 5 drugs (CFTM, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), erythromycin (EM], against stock strains and MICs of 6 drugs (CFTM, CEX, CCL, ABPC, methicillin, cloxacillin) against fresh strains from patients received to CFTM-PI, with an inoculum size of 10(6) cfu/ml. A total of 149 strains included Gram-positive cocci i.e. Staphylococcus aureus (11), Streptococcus pyogenes (85), Streptococcus agalactiae (16) and Streptococcus pneumoniae (4), and Gram-negative rods i.e. Haemophilus influenzae (11), Bordetella pertussis (11), Escherichia coli (9), Proteus mirabilis (1) and Morganella morganii (1). The granular form of CFTM-PI was administered to 9 boys (age: 8 years 3 months approximately 10 years 10 months) to determine serum and urinary concentrations of the drug and its urinary recovery rates using bioassay. Doses of 1.5, 3.0 and 6.0 mg/kg were given orally 30 minutes after meal to 3 boys, respectively. Urinary concentrations and its urinary recovery rates of T-2525A, a main metabolite of CFTM, were determined using high performance liquid chromatography (HPLC). To study clinical and bacteriological effects of this drug, a mean daily dose of 3.3 mg/kg divided 3-4 times a day (3 times: 133 cases, 4 times: 9 cases) was administered for 8 days on the average to a total of 142 cases with pharyngitis (22), tonsillitis (12), acute bronchitis (3), pneumonia (11), pleurisy (1), scarlet fever (28), acute purulent otitis media (16), impetigo (13), abscess (2), purulent lymphadenitis (1) and urinary tract infection (33). Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients. The results obtained are summarized as follows. 1. With regard to Gram-positive cocci, MICs of CFTM against 11 fresh strains of S. aureus ranged from 3.13 to 6.25 micrograms/ml except for 1 strain, thus CFTM was equally effective to CEX, but less active than the other drugs tested.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic, bacteriological and clinical studies on sulbactam/ampicillin in pediatric field

Clinical trials were carried out on the use of sulbactam/ampicillin (SBT/ABPC) (combination rate of 1:2) in pediatric infections. Results were as follows: 1. The mean half-lives of SBT and ABPC in the serum following intravenous injection of SBT/ABPC were about 1.05 and 0.90 hours, respectively. 2. The mean urinary excretions of SBT and ABPC in 6 hours after intravenous injection of SBT/ABPC were 71.2% and 62.2%, respectively. 3. SBT/ABPC was administered to 23 pediatric patients with various infections: 17 patients with pneumonia, 3 with tonsillitis, 2 with urinary tract infection and 1 with cervical lymphadenitis. The overall efficacy rate was 95.7%. In particular, 2 urinary tract infections caused by highly beta-lactamase producing Escherichia coli were improved by the treatment with SBT/ABPC. 4. No adverse reactions were observed except 2 cases of mild diarrhea. Abnormal laboratory test values included thrombocytosis in 4 and slight elevation of GOT and GPT in 1, but they were transient.     

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium in the pediatric field

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a newly developed combined antibiotic in a 1:1 ratio, were performed in the field of pediatrics. The MK-0787/MK-0791 was administered to 15 children. Ten and 20 mg/kg doses of MK-0787 were administered by a intravenous drip infusion for 30 minutes to 3 children each. In the remaining 9 cases, MK-0787 doses of 10, 20 and 30 mg/kg were administered to 3 children each by a 1 hour intravenous drip infusion. Levels of MK-0787 and MK-0791 in plasma, urine and urinary recovery rate of the drugs were also determined. In addition, MK-0787/MK-0791 was administered to a total of 29 children; 2 children with bronchitis, 16 with pneumonia, 4 with UTI, 2 with purulent lymphadenitis and 1 child each with tonsillitis, septicemia suspected disease, peritonitis, staphylococcal scalded skin syndrome and osteomyelitis/bacteremia. The average single dose was 15.3 mg/kg of MK-0787 and administrations were performed by 20-60 minutes intravenous drip infusion 3-4 times daily for an average period of 6 days. The clinical and bacteriological effects of this drug were evaluated in these cases and adverse reactions and unusual laboratory findings were also studied in a total of 33 cases including 4 other drop-out cases. Results of these studies were summarized as follows. In 6 children, 3 each who were given doses of 10 or 20 mg/kg, the mean peak plasma concentrations of the drugs were found at the end of the 30 minutes-infusion with values of 35.20 and 74.90 micrograms/ml for MK-0787 and 44.85 and 93.32 micrograms/ml for MK-0791 after the dose of 10 and 20 mg/kg, respectively. The peak plasma levels of MK-0791 were approximately 1.3 times higher than those of MK-0787 and higher peak levels were observed in the groups with larger doses of either drugs. In the 10 mg/kg group, the mean half-lives of MK-0787 and MK-0791 were 0.97 and 0.71 hour, respectively and those values were 0.89 and 0.63 hour, respectively in the 20 mg/kg group. In both group, MK-0787 tended to have longer half-lives than MK-0791. In 9 children, 3 each who were administered doses of 10, 20 and 30 mg/kg by a 1 hour intravenous drip infusion had the highest plasma levels for both MK-0787 and MK-0791 at the end of the infusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on cefodizime in the pediatric field. Pediatric Study Group of Cefodizime

A multi-center open study was conducted to investigate cefodizime (CDZM), a newly developed cephem antibiotic, from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows: 1. Serum concentrations and urinary excretion: The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg, via a bolus intravenous injection or intravenous drip infusion over 30 or 60 minutes. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after a bolus intravenous injections were: 105.5, 264.0 and 461.7 micrograms/ml with 10, 20 and 40 mg/kg, respectively, and T 1/2 (beta)'s for the 3 dosages were 1.75, 1.92 and 1.88 hours, respectively. With 30-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 90.5 micrograms/ml with a dose level of 10 mg/kg, 178.3 micrograms/ml with 20 mg/kg, and 322.8 micrograms/ml with 40 mg/kg, and T 1/2 (beta)'s for these dosages were 1.90, 2.15 and 1.93 hours, respectively. With 60-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 66.3 micrograms/ml with a dose level of 10 mg/kg, 136.0 micrograms/ml with 20 mg/kg and 259.2 micrograms/ml with 40 mg/kg, and T 1/2 (beta)'s for these dosages were 1.43, 2.05 and 1.46 hours, respectively. In 8 hours after administration of CDZM, urinary excretion rates were 82.1, 77.7 and 76.5% for bolus intravenous injections of 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively, and 83.3, 71.3 and 68.1% for 30-minute intravenous drip infusions of 10 mg/kg, 20 mg/kg and 40 mg/kg, and 84.4 and 84.3% for 60-minute intravenous drip infusions of 20 mg/kg and 40 mg/kg, respectively. 2. Concentrations in cerebrospinal fluid: Penetrations into cerebrospinal fluid in patients with purulent meningitis reached levels of 1.96-9.48 micrograms/ml with administration of CDZM at 50 mg/kg in acute cases within 6 days after onset. The penetration rates of CDZM were about a median range among injectable beta-lactam agents. 3. Clinical results: Of 457 cases treated with CDZM, 53 cases were excluded from the clinical evaluation. Clinical efficacies were evaluated as "excellent" in 126 and "good" in 78 out of 221 case from which causative agents were isolated, with an efficacy rate of 92.3%. Efficacies were "excellent" in 97 and "good" in 69 out of 183 cases from which pathogens were not isolated giving an efficacy rate of 90.7%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical evaluation of cefpirome in the pediatric field

We conducted a pharmacokinetic and clinical study on cefpirome (HR 810, CPR), an aminothiazolylmethoxyiminoacetamido cephalosporin (ATOIC), and obtained the following results. 1. Concentrations in blood/excretion in urine. We studied pharmacokinetic in children upon intravenous bolus injections and 30-minute and 1-hour intravenous drip infusions in single dosages of 10, 20, and 40 mg/kg, and obtained virtually the same results as those found in adult subjects. Upon intravenous bolus injections, mean blood concentrations 30 minutes after administration of 10, 20, and 40 mg/kg were 26.1, 47.8, and 82.8 micrograms/ml, respectively, and half-lives were 1.13, 1.43, and 1.26 hours, respectively. Upon 30-minute intravenous drip infusion, mean blood concentrations on completion of the drip infusions of 10, 20, and 40 mg/kg were 43.2, 106.9, and 163.0 micrograms/ml, respectively, and half-lives were 1.15, 1.09, and 1.15 hours, respectively. In addition, upon 1-hour intravenous drip infusion, mean blood concentrations on completion of infusion were 27.1 micrograms/ml for 10 mg/kg and 47.5 micrograms/ml for 20 mg/kg, and half-lives were 1.09 and 1.40 hours, respectively. A clear dose response was observed at all dosages for either administration method. Mean excretion rates in urine in the first 8 hours after administration were 60.6-71.1% upon intravenous bolus injections of 10-40 mg/kg, and upon intravenous drip infusion, the values were 50.2-83.8% for administration of 10-40 mg/kg 6 or 7 hours after completion of drip infusion. 2. Concentrations in the cerebrospinal fluid Penetration into the cerebrospinal fluid was studied in 2 subjects, and a concentration of 0.28-5.19 micrograms/ml was observed upon administration of 50 mg/kg, a moderate degree of penetration compared to the penetration of cephalosporins of group 5 studied up to now. 3. Clinical results Evaluation of clinical effects of CPR on various types of bacterial infections was conducted in 56 subjects, excluding 3 subjects who had diseases which were excluded from the study. The breakdown was as follows: 3 cases of meningitis, 1 case of septicemia, 25 cases of bronchial pneumonia, 1 case each of tonsillitis and infection of the external acoustic meatus, 2 cases each of scarlet fever and phlegmon, 8 cases each of lymphadenitis and urinary tract infections, and 5 cases of staphylococcal scalded skin syndrome. Results of excellent or good were obtained in 54 subjects for an efficacy rate of 96.4%.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Pharmacokinetic and clinical studies on cefodizime in gynecologic field

Pharmacokinetic and clinical studies on a new cephalosporin antibiotic, cefodizime (THR-221, CDZM), were performed and the results obtained are summarized as follows: 1. At about 84 minutes after a bolus injection of 1 g dose of CDZM, the drug was transferred well into tissues of internal genital organs and remained there at therapeutic levels for 285 minutes. The drug was also transferred quickly and sufficiently into exudate from pelvic dead space and its levels were still kept at high levels at 6 hours after administration. 2. CDZM was given to 8 women affected with gynecologic infections. The outcome of CDZM therapies showed that the drug was effective in all 8 of patients (100%) clinically and bacteriologically. 3. Notable adverse effects or abnormal laboratory test results were not observed except for 2 patients with transient and slight elevation of transaminase levels. Based on these results, it may be concluded that CDZM is a highly effective and a very safe antibiotic for the treatment on infectious diseases in gynecologic field.     

Pharmacokinetic and clinical studies of cefdinir in the pediatric field. Pediatric Study Group of Cefdinir]

We studied pharmacokinetics and clinical effects of 5% and 10% fine granules of cefdinir (FK 482, CFDN), a new oral cephalosporin, in the pediatric field and the following results were obtained. 1. Pharmacokinetics (blood concentration and urinary excretion) Pharmacokinetics of CFDN in 163 children was investigated. Cmax and T 1/2 were 0.92 +/- 0.45 micrograms/ml and 1.95 +/- 1.06 hours, respectively, in the fasting state, and were 0.63 +/- 0.29 micrograms/ml and 2.26 +/- 0.65 hours, respectively, in the non-fasting state, at a dose level of 3 mg (potency)/kg. At a dose level of 6 mg (potency)/kg, Cmax and T 1/2 were 1.29 +/- 0.49 micrograms/ml and 2.11 +/- 1.85 hours, respectively, in the fasting state and were 1.28 +/- 0.48 micrograms/ml and 2.01 +/- 0.84 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that blood concentration of the drug depended on dose levels. Urinary recovery rates in the first 8 hours were 20.5 +/- 8.8% in the fasting state and 14.8 +/- 5.9% in the non-fasting at a dose level of 3 mg (potency)/kg and 16.5 +/- 6.7% and 17.8 +/- 2.4%, respectively, at 6 mg (potency)/kg. 2. Clinical effects Clinical effects of CFDN on various infections were studied in 612 children who were treated with 5% fine granules of CFDN (5% granule group) and in 208 with 10% fine granules of CFDN (10% granule group). CFDN granules were administered mainly at daily doses of 9.0-18.0 mg (potency)/kg in 3 divided portions. Clinical efficacy rates in 428 children of the 5% granule group and in 159 of the 10% granule group from whom causative bacteria were isolated, were 94.9% and 96.2%, respectively. The clinical efficacy rates for patients who were responsive to previous antibiotic therapy were 91.2% in the 5% granule group and 100% in the 10% granule group. Bacteriological eradication rate was 82.1% for 491 strains in the 5% granule group, and was 84.0% for 175 strains in the 10% granule group. The incidences of side effects were 3.9% (24/608) in the 5% fine granule group and 5.8% (12/206) in the 10% granule group. All of the side effects were slight gastrointestinal disorders, and no serious side effects were found. As for clinical laboratory test results, slight elevations of eosinophile, platelet or transaminase were observed. Based on the above results, it is considered that the appropriate dose levels of CFDN for pediatric infections ranged from 9.0 to 18.0 mg (potency)/kg a day, divided into 3 portions.