Biomedical subjects

T Motohiro

Publications and source records attributed to T Motohiro.

At least 55 records · Page 3Linked to original sources

PubMed1990

[Effect of BMY-28100 on bacterial flora in adult human feces].

We investigated effects of BMY-28100 on fecal bacteria. BMY-28100 was administered orally to 8 healthy male volunteers between 20 and 24 years of age weighing between 58.0 and 79.5 kg. All subjects were given one 250 mg capsule 3 times a day at 30 minutes after meal for 7 days. Fecal bacterial counts were examined 5 days before the start of administration, the day of the start of administration, 3, 5 and 7 days after the start of administration, and 3, 5, 10, 20 and 30 days after the end of administration. Concentrations of BMY-28100 and Clostridium difficile D-1 toxin in feces were also examined together with examinations for adverse reactions and abnormal laboratory test values. 1. Total aerobic bacterial counts increased transiently upon the antibiotic dosage. Escherichia coli and yeast like organism increased transiently during the period of administration, while the total counts of anaerobic bacteria remained constant. Veillonellaceae, Peptococcaceae and Eubacterium decreased transiently during the period of administration. Although C. difficile and its D-1 toxin were detected in 1 and 5 cases, respectively, these feces appeared normal. 2. Active metabolites of BMY-28100 were not detected in the feces. 3. No adverse effects or no abnormal laboratory test values were observed.

Administration, Oral↗

PubMed1990

[Effect of rokitamycin on bacterial flora in human feces].

Rokitamycin, a newly developed macrolide antibiotic was orally administered to 7 healthy male volunteers (22-25 years) for 7 consecutive days to study changes in bacterial flora and concentrations of the drug in feces, and to observe adverse reactions and laboratory test parameters. A dose of 200 mg (2 tablets: 100 mg/tablet) was given 3 times daily before meals and the fecal studies were done on the 5 days before administration (adm.) [b.a.], at the time of administration (0), and the 3rd, 5th, 7th (the final day of treatment) days during adm. [u.a.] and the 3rd, 5th, 10th, 20th, 30th days after adm. [a.a.]. The results obtained are summarized as follows. 1. Obvious changes in mean populations of total aerobes and enterobacteriaceae were not found. In changes of each bacteria of enterobacteriaceae, Escherichia coli was not observed in cases from initial day of treatment to the 3rd day a.a. Cases from which Citrobacter sp. was isolated tended to increase after 3 days u.a. and gradually decrease after 3 days a.a. Among Gram-negative bacilli, cases where isolation of Pseudomonas sp. was observed increased temporarily on the 3rd u.a., Gram-positive cocci did not show particular patterns of changes. No changes in mean count of total anaerobes were observed during the course of the experiment. Among individual anaerobes, numbers of Lactobacillus and Peptococcaceae decreased slightly from the 3rd day u.a. and returned on the 5th day a.a. 2. Clostridium difficile D-1 toxin was detected in feces at amounts approximately 500 ng/g in 2 cases each on 20th and 30th day a.a., with 1 incidence occurring in the same person on the 2 separate days. 3. The drug was detected in all 7 cases on the 3rd, 5th and 7th days u.a., and in 1 cases each on the 5th and the 30th day a.a. The mean peak level was 315.5 micrograms/g on the 7th day u.a. The reason for the detection of the drug in feces in 1 case on the 30th day a.a. at a value of 5.90 micrograms/g was not clear. 4. Adverse reactions and abnormal laboratory test results due to this drug were not observed in any cases.

Administration, Oral↗

PubMed1990

[Pharmacokinetic and clinical evaluations of aztreonam monotherapy and aztreonam and ampicillin combination therapy in neonates and premature infants].

One-shot intravenous injection of aztreonam (AZT), a monobactam-class beta-lactam antibiotic, 20 mg/kg was administered to 4 neonates and 2 premature infants, a total of 6 cases, and plasma and urinary concentrations and urinary recovery rates were determined. Also, one-shot intravenous injection averaging 70.9 mg/kg/day of AZT alone was given to 0- to 43-day neonates and premature infants in b.i.d. to q.i.d. for an average of 8 days for the treatment (6 cases) and prophylaxis (11 cases) of infections. Furthermore, a combination therapy of AZT and ampicillin (ABPC) was applied to 0- to 79-day neonates and premature infants for the treatment (28 cases) and prophylaxis (18 cases) of infections. Average daily dosage of AZT 46.6 mg/kg was given by one-shot intravenous injection or by drip infusion in b.i.d. or t.i.d. for an average of 8 days. Average daily dosage of ABPC 78.6 mg/kg was given in the same daily frequency, route and average duration as AZT. Thus, clinical effects, prophylactic effects against infection, bacteriological effects as well as side effects and clinical laboratory test values were studied with the following results. 1. When AZT 20 mg/kg was administered to 1 case each of 6- and 7-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 5 minutes after the administration in both cases. Specifically, they were 62.9 and 72.7 micrograms/ml with AUCs of 216.6 and 231.6 micrograms.hr/ml and half-lives of 2.80 and 2.97 hours, respectively. When AZT 20 mg/kg was administered to 5- and 6-day premature infants by one-shot intravenous injection, the plasma concentrations were the highest at 15 minutes after administration in the former and 5 minutes in the latter, at values of 59.8 and 67.7 micrograms/ml, respectively. AUCs were 356.6 and 363.2 micrograms.hr/ml, respectively, and larger than AUCs of the above-mentioned neonates. Half-lives were 5.74 and 4.87 hours, respectively and longer than those of the above-mentioned neonates. When AZT 20 mg/kg was administered to 8- and 13-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 30 minutes after administration in the former and 5 minutes in the latter, at values of 43.4 and 76.9 micrograms/ml, respectively. AUCs were 202.9 and 189.8 micrograms.hr/ml, and 76.9 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Ampicillin↗

PubMed1989

[Clinical study on clarithromycin granule and tablet in the field of pediatrics].

A newly developed macrolide clarithromycin (TE-031, A-56268), with antibacterial spectrum and antibacterial activity nearly equal to those of erythromycin (EM), shows beneficial characteristics such as a higher blood level, higher recovery rate in urine, and better penetration into each tissue than conventional macrolides (MLs). TE-031 has been studied in adults against various infections and proved to be useful. The present paper describes the results of a study in children to examine the usefulness of TE-031 granules and tablets with a potency of 50 mg. TE-031 granules were administered to 132 children with ages from 6 months to 13 years and 10 months. Excluded from the evaluation were 12 cases in which clinical effects were deemed unevaluable. The evaluable subjects consisted of 1 case with pharyngitis, 3 with tonsillitis, 9 with acute bronchitis, 19 with pneumonia, 19 with mycoplasmal pneumonia, 2 with scarlet fever, 20 with Campylobacter enteritis, 11 with impetigo, 2 with subcutaneous abscess, 18 with primary atypical pneumonia and 16 with acute enteritis of unidentified pathogens; a total of 120 subjects. An average daily dose of TE-031 was 25.9 mg/kg, divided into 3 doses except 1 case with 2 daily doses and lengths of the treatment averaged 7 days. TE-031 tablets each containing 50 mg potency, were administered to 49 subjects with ages from 3 year and a month to 14 years consisting of 8 cases with pharyngitis, 1 with tonsillitis, 1 with acute bronchitis, 4 with pneumonia, 14 with mycoplasmal pneumonia, 4 with scarlet fever, 5 with Campylobacter enteritis, 7 with impetigo, 1 with atypical pneumonia, 1 with Salmonella gastroenteritis and 3 with acute enteritis caused by unidentified pathogens, at an average daily dose of 13.5 mg/kg dived into 2-4 doses (2 doses/day for 12 cases, 3 doses for 32, 4 doses for 5) for 7 days on the average. In addition to examine the clinical and bacteriological effects of the 2 dosage forms of TE-031, minimum inhibitory concentrations (MICs) were determined for 9 antibiotics consisting of 5 MLs including TE-031, EM, josamycin (JM), midecamycin acetate (MDM acetate), and rokitamycin (RKM), 3 penicillins including ampicillin (ABPC), methicillin, cloxacillin and 1 cephem antibiotic, cefaclor (CCL), against 29 strains consisting of 12 strains of Staphylococcus aureus, 7 of Streptococcus pyogenes, 2 of Streptococcus pneumonia 2 of Haemophilus influenzae and 6 of Campylobacter jejuni, out of 71 strains of pathogens or possible pathogens that had been isolated from the cases given TE-031.

Age Factors↗

PubMed1989

[Pharmacokinetics of clarithromycin granule and tablet in children].

It has been known that clarithromycin (TE-031, A-56268), a new macrolide antibiotic (ML), achieves higher concentrations in blood, is better excreted into urine and is better distributed into various tissues than conventional MLs. We investigated the pharmacokinetics of TE-031 in children upon oral administration of the drug in the following method. TE-031 granular preparation with a potency of 100 mg/g was given to 6 boys (5 years 4 months-14 years 0 month) with dose levels of 5 mg/kg and 10 mg/kg for each 3 boys. A tablet preparation with each tablet containing 50 mg of TE-031 was administered to 4 boys and 2 girls (8 years 5 months-11 years 6 months) with dose level of 2 tablets (i.e., 100 mg) and 3 tablets (i.e., 150 mg) for each 3 children. All administrations were done at 30 minutes before meal. Then, to conduct a cross-over test, the granule preparation was given orally to the 3 children mentioned above who was given 2 tablets and the 1 of 3 cases that were given 3 tablets at the same dose levels (100 mg and 150 mg) respectively. A bioassay was used to determine concentrations in blood of active antibiotic compounds and an high performance liquid chromatography (HPLC) was used to determine unchanged TE-031 and its main metabolite, M-5. Urinary concentrations of active antibiotic compounds were also determined by the bioassay and the HPLC was used to determine concentrations and proportions of unchanged TE-031 and its metabolites, M-1, M-4, M-5, M-6 and M-7 to figure out the urinary recovery rate in the first 6 hours. The results of these experiments are summarized as follows. 1. As was mentioned above, TE-031 was administered orally to 2 groups of children at dose levels of 5 mg/kg and 10 mg/kg, respectively. Mean serum levels of total active antibiotic compounds reached their maximum in 1 and 2 hours for the 5 mg/kg and the 10 mg/kg dosage groups, respectively, at 1.28 and 3.62 micrograms/ml, respectively. Mean half lives of serum concentrations in the 2 groups were quite similar, with values of at 2.1 and 2.0 hours, respectively. Mean serum concentrations of unchanged TE-031 determined by the HPLC method reached their peaks in 1 hour after administration in either of the 5 and 10 mg/kg dosage groups at peak levels of 0.65 micrograms/ml and 2.67 micrograms/ml, respectively. Thus, dose-response relationships were observed with TE-031 and M-5.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1989

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and premature infants].

Cefmenoxime (CMX) was administered by intravenous bolus injection to a total of 23 neonates and premature babies with aged 1 to 26 days at a dose of 10 or 20 mg/kg and their plasma and urine concentrations and urinary recovery rates were determined up to 6 hours after administration. In addition, for the treatment of bacterial infections, diagnosed or suspected, or for the prophylaxis of bacterial infections, the drug was administered to a total of 27 neonates, premature babies and infants, with ages of 0 day to 3 months. It was possible to evaluate therapeutic efficacy and prophylactic efficacy in 15 cases and 7 cases, respectively. In these cases, side effects and bacteriological effects and, in some of them, changes in laboratory test values were also investigated. The obtained results are summarized below. 1. At a dose level of 10 mg/kg (n = 7), peak plasma concentrations at 5 minutes after administration, were 42.6 microns/ml in neonates with ages of 15 to 21 days and 45.9 microns/ml in those with ages of 22 to 28 days in a group of less than 2,500 g b.w. (birth weight), and 36.9 microns/ml in neonates with ages of 4-7 days and 38.9 microns/ml in those of 8-14 days in the other group of greater than of equal to 2,500 g b.w., indicating no large differences among the 4 subgroups (each of the above concentration values is either the value for an individual when only one neonates was involved or a mean value when 2 or more neonates were involved. The same applies hereinafter). Though 1 exceptional case showed a biphasic change, its cause is unknown. Half-lives in the above-mentioned 4 subgroups were 1.5, 1.6, 2.4 and 1.9 hours, respectively. The half-life of 2.4 hours in 1 patient with an age of 5 days of the greater than or equal to 2,500 g b.w. group was longer than in any of the other 3 subgroups. 2. At 20 mg/kg (n = 16) dosage level, mean peak plasma concentrations were 63.8 microns/ml in the infants of 0-3 days, 68.1 microns/ml in those of 8-14 days and 59.4 microns/ml in those of 15-21 days in the group of less than 2,500 g b.w., and 109.9 microns/ml in the neonates aged 8-14 days and 79.7 microns/ml in those of 15-21 days in the group greater than or equal to 2,500 g b.w.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

PubMed1989

[Fundamental and clinical studies of cefsulodin in the neonates and premature infants].

Fourteen neonates and premature infants with ages ranging 1 to 28 days were intravenously given one shot injection of 20 mg/kg of cefsulodin (CFS). Plasma and urine levels and recovery rates of CFS were determined in the first 6 hours after administration. For prophylaxis of infection, a daily average dose of 52.8 mg/kg of CFS was injected intravenously to 3 neonates with ages ranging 2 to 16 days in 2 to 3 divided doses during an average period of 7 days. Along with observations of prophylactic effects on infection, side effects and abnormalities in laboratory test values were examined. The results obtained are summarized below: 1. Of the 9 patients with birth weight of 2,500 g or above, the plasma levels peaked in 6 patients at 5 minutes, in 2 patients at 15 minutes and in the other at 1 hour after administration, with peak levels ranging between 35.8 and 60.6 micrograms/ml. Subsequently, gradual decreases or bimodal tapering changes were noted in the plasma levels. The cause of the delay in the occurrence of maximum peak observed in the 3 patients at 15 minutes or 1 hour after administration and the cause of the appearance of bimodal tapering changes in 3 subjects are not known. A tendency was observed that the younger the age of subject was, the larger the AUC and the longer the half-life became. Half-lives in all 9 neonates were longer than those in average infants who were given intravenous injection at the same dose. 2. Of 5 patients with birth weight of less than 2,500 g, the determination of peak plasma levels was not performed in those within 7 days after birth. Plasma levels, however, were observed to reach their peaks in 4 patients at 5 minutes and in another at 15 minutes after administration, the levels ranging between 41.5 and 56.0 micrograms/ml. Subsequently to this, gradual decreases and bimodal tapering changes of plasma levels were noted. The cause of the delay in plasma levels to reach their maximum peaks values in the 1 patient to 15 minutes after administration and the cause of occurrence of bimodal tapering changes in the 2 patients are not known. A tendency was observed that the younger the age of subjects was, the larger the AUC and the longer the half-life became. This tendency was similar to that observed in the group with birth weight of 2,500 g or above.(ABSTRACT TRUNCATED AT 400 WORDS)

Cefsulodin↗

PubMed1989

[Pharmacokinetic, bacteriological and clinical studies of sulbactam/ampicillin in pediatric patients].

Plasma and urine concentrations of sulbactam (SBT) and ampicillin (ABPC) were determined following bolus administration of injectable SBT/ABPC combined in a fixed ratio of 1:2 to 6 pediatric patients, 3 at a dose of 30 mg/kg and the other 3 at 60 mg/kg. Clinical and bacteriological efficacies of SBT/ABPC were evaluated in a total of 65 patients composed of 45 cases with pneumonia, 3 cases each with bronchitis, urinary tract infections, staphylococcal scalded skin syndrome, purulent lymphadenitis, 2 cases each with tonsillitis, pleuropneumonia, phlegmon and 1 case each with pyothorax, submaxillitis. The dosage used was 101.2 mg/kg daily given in 3 or 4 divided doses (t.i.d. in 24 patients and q.i.d. in 41 patients) by bolus intravenous injection for 7 days on an average. Side effects and effects on clinical laboratory parameters were monitored in the 65 patients. The results of these evaluations are summarized as follows. 1. Mean serum concentrations of SBT and ABPC in 3 children each given an intravenous bolus injection of 30 mg/kg and other 3 each given 60 mg/kg reached peak levels at 5 minutes after administration with values of 49.8 and 90.3 micrograms/ml, respectively, for SBT and 99.8 and 189.7 micrograms/ml, respectively, for ABPC. The latter values were about twice as high as SBT, and both were dose-related. Mean half-lives were 0.889 hour for SBT and 0.857 hour for ABPC in the 30 mg/kg group and 0.882 hour for SBT and 0.834 hour of ABPC in the 60 mg/kg group, showing similarities between the 2 dosage groups as well as between SBT and ABPC. 2. Mean urine concentrations in the 2 groups mentioned above were the highest for both SBT and ABPC during the first 2 hours after administration, with values of 1,677 micrograms/ml for SBT and 2,730 micrograms/ml for ABPC in the 30 mg/kg group and 2,693 micrograms/ml and 3,623 micrograms/ml, respectively, in the 60 mg/kg group. Mean recovery rates in urine in the first 6 hours were 72.4% for SBT and 56.8% for ABPC in the low dosage group and 72.7% and 52.0%, respectively, in the high dosage group. In the 2 groups, the amounts of ABPC recovered were less than those of SBT. 3. Clinical efficacies of SBT/ABPC in 65 patients with various bacterial infections were excellent or good in 62 (95.4%) patients. 4. The bacteriological efficacy was evaluable with 10 patients. The pathogenic bacteria were eradicated in 9 patients and the efficacy rate was 90%.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1989

[Pharmacokinetic and clinical evaluations of imipenem/cilastatin sodium in neonates and premature infants].

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic of the carbapenem class and its renal dehydropeptidase-I inhibitor in a 1:1 ratio, were performed in neonates, premature infants and an infant. IPM/CS was administered intravenously to 4 neonates and 5 premature infants at a dose level of 10 mg/kg. Plasma levels and urinary excretion of IPM and CS were determined in 2 neonates and 2 premature infants after 30-minute infusion, and in 2 neonates and 3 premature infants after 1-hour infusion. Plasma and cerebrospinal fluid (CSF) concentrations of IPM and CS were determined in 2 cases with purulent meningitis with ages of 2 and 26 days and 1 with purulent meningitis/bacteremia with an age of 4 days. The drug was administered to a total of 31 patients with ages between 0 and 30 days, consisting of neonates, premature infants and an infant (24 suffering with various bacterial infections, 5 treated for prophylaxis of infections and 2 treated for aseptic meningitis diagnosed at the completion of therapy) by intravenous drip infusion in a mean daily dose level of 50.1 mg/kg in 2 to 4 divided doses for 9 days on the average. Clinical efficacy, prophylactic effectiveness and bacteriological response of IPM/CS were evaluated in 29 cases. Adverse effects and abnormal laboratory test results were examined in 31 cases including 2 drop-out cases. The results obtained are summarized as follows. 1. Plasma concentrations of IPM and CS after 30-minute infusion of the drug reached their peaks at the end of administration, and obtained values were 22.4 to 29.0 micrograms/ml for IPM and 26.3 to 34.6 micrograms/ml for CS, thus peak plasma levels of CS were a little higher than IPM. Plasma half-lives of IPM were 1.05 to 2.43 hours, and those of CS were 1.24 to 4.76 hours, and the half-life of CS tended to be longer than that of IPM. Drug concentrations in plasma after 1-hour infusion of IPM/CS reached their peaks at the end of administration and the levels of CS (25.7 to 32.0 micrograms/ml) were a little higher than those of IPM (20.8 to 23.9 micrograms/ml). Plasma half-lives of IPM were 1.40 to 1.63 hours, whereas those of CS were 1.51 to 2.90 hours. The half-life of CS tended to be longer than IPM. 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

PubMed1989

[Pharmacokinetic and clinical studies on cefpodoxime proxetil dry syrup in the field of pediatrics].

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 10(8) and 10(6) 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1989

[Clinical study of cefpodoxime proxetil dry syrup for skin and soft tissue infections in the field of pediatrics].

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 10(6) and 10(8) 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 10(8) cfu/ml showed 2 peaks of MIC values, one in a range of 1.56 to 6.25 micrograms/ml and the other higher than 100 micrograms/ml. The most prevalent MIC value was 3.13 micrograms/ml with MIC against 51 strains or 71.8% of the strains tested showing this value, and MIC values of 25 micrograms/ml or higher were obtained for 13 strains or 18.3% of the strains tested. The MIC80 was 6.25 micrograms/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 10(6) cfu/ml also had 2 peaks, one in a range of 1.56 to 3.13 micrograms/ml and the other higher than 25 micrograms/ml. Strains against which R-3746 had the MIC value of 3.13 micrograms/ml were the most numerous with 47 strains or 66.2%, and strains against which the MIC value of higher than 25 micrograms/ml was obtained were next with 13 strains or 18.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

PubMed1989

[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)

Bacterial Infections↗

PubMed1988

[Microbiological, pharmacokinetic and clinical studies of rokitamycin dry syrup in the pediatric field].

Rokitamycin (RKM), a newly developed macrolide antibiotic with a 16-membered ring, dissolves well under acidic conditions. It has been improved over other macrolides to minimize individual variations in its absorbability. We measured, using the GA-test, variations in gastric acidities of 43 children with ages between 1 to 14 years, and investigated the relationship between gastric acidities and pharmacokinetic values. Also activities (expressed in MICs) of antimicrobial agents were studied against clinically isolated 229 bacterial strains using an inoculum size of 10(6) cells/ml. Tested organisms included Streptococcus pyogenes (77 strains), Streptococcus agalactiae (29), Streptococcus pneumoniae (2), as Gram-positive cocci, and Haemophilus influenzae (1), Haemophilus parainfluenzae (1), Bordetella pertussis (12), Salmonella sp. (4) and Campylobacter jejuni (103) as Gram-negative bacilli. Against stock strains of bacteria, MICs of 10 drugs (RKM, erythromycin (EM), josamycin (JM), midecamycin (MDM), midecamycin acetate (MOM), clindamycin (CLDM), amoxicillin (AMPC), cefaclor (CCL), minocycline, ofloxacin (OFLX] were determined. Against isolates from patients who underwent treatment with RKM, MICs of only 4 drugs (RKM, EM, JM, MOM) were determined. Measurements were made on plasma and urinary concentrations of RKM and its urinary recovery rates after patients including 6 boys with ages between 5 years 1 month and 11 years 6 months were administered with RKM (dry syrup). Two groups of 6 boys were administered between meals with RKM at dose levels of 5 and 10 mg/kg, respectively. Clinical and bacteriological effects of RKM were evaluated for 175 patients including 5 cases of pharyngitis, 3 tonsillitis, 32 pneumonia, 17 mycoplasmal pneumonia, 34 atypical pneumonia, 28 streptococcal infections, 29 Campylobacter enteritis, 4 Salmonella gastroenteritis, and 23 enteritis due to unknown organisms. Five drop-out cases were excluded from the evaluations. In the evaluable cases, an average dose level used was 31.8 mg/kg/day, with a daily dose divided into 3 to 4 administrations and with an average treatment duration of 9 days. Adverse reactions of RKM and its effects on laboratory test values were investigated in these patients including the drop out cases. Obtained results of these studies are summarized below. 1. The GA-test produced pH values indicating that amounts of gastric acid were mostly either normal or high in 42 of the 43 subjects tested (97.7%), and only one low acid case (2.3%) was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1988

[Pharmacokinetic and clinical studies on the use of ceftizoxime in premature and newborn infants. The Chemotherapy Research Group for Mother and Child].

A pharmacokinetic and clinical study of ceftizoxime (CZX), a newly developed cephem antibiotic intended for parenteral use, was conducted in premature and newborn infants, and resulted in the following findings. 1. Pharmacokinetics (1) Average serum half-lives (T 1/2) following a one shot intravenous dose of 20 mg/kg of CZX to mature and premature newborn infants in age groups of 0-3, 4-7, 8-14, and 15-30 days were: 4.14, 3.01, 2.57, and 1.98 hours (for mature infants) and 5.26, 4.59, 3.71, and 2.64 hours (for premature infants), respectively, decreasing with ages in days of the infants. (2) Average T 1/2's after a one shot 10 mg/kg dose was similar to that after a 20 mg/kg dose. Serum concentrations of CZX were dose-dependent. (3) T 1/2 after 1-hour intravenous drip infusion revealed a same trend after one shot injection. (4) Urinary in the first approximately 6 hours recoveries following a 20 mg/kg one shot dose to mature and premature newborn infants were as follows: 35% (0-3 days old) and 45-55% (4 days old and older) in mature infants and 30% (0-3 days old) and 45% (4 days old and older) in premature infants. 2. Therapeutic effectiveness (1) The subjects examined were 112 newborn infants consisting of 83 with infections and 29 who received CZX for prophylaxis. The 83 infants had 86 cases of infections, which were classified as A, when the causative organisms were identified and as B, when the causative organisms were not identified. Rates of therapeutic effectiveness were 95.0% for group A and 95.7% for group B. Bacteriological effectiveness were studied on 41 strains isolated from group A, and were as high as 89.5% for Gram-positive organisms and 95.5% for Gram-negative organisms. The rate of successful prophylaxis for the 29 infants was 96.6%. (2) Side effects did not occur among the 120 newborn infants. Laboratory tests with abnormalities included leukopenia, neutropenia, eosinophilia, thrombocytosis and increased GOT or GPT. These pharmacodynamic and clinical findings have fully substantiated the satisfactory therapeutic usefulness of CZX in both the treatment and prevention of neonatal infections in the usual dose of 20 mg/kg, which is to be given b.i.d. for infants up to 3 days old; b.i.d. or t.i.d. for infants 4 to 7 days old, and t.i.d. or q.i.d. for infants 8 days old and older. The drug can be given in a daily dose as high as 120 mg/kg when infection is severe.

Bacterial Infections↗

PubMed1988

[Pharmacokinetic, bacteriological and clinical studies of ceftizoxime in neonates and low birth weight infants].

Ceftizoxime (CZX), one of the fifth group in cephem-antibiotics classified by Fujii, was administrated intravenously with a one shot dose of 20 mg/kg to neonates and low birth weight infants with ages ranged 4-21 day old and plasma and urinary concentrations and urinary recovery rates of the drug were determined. Clinical, prophylactic and bacteriological effects of CZX were evaluated and adverse reactions and effects on laboratory test values due to this drug were studied in 22 neonates and low birth weight infants (0-76 day old) consisting of 16 cases with various bacterial infections including presumptive cases of bacterial infections and 6 cases with prophylactic administration against infectious diseases. An average CZX daily dose of 55.3 mg/kg was given once or divided into 2-4 times daily (twice: 16 cases, 3 times: 3 cases, 4 times: 2 cases) through intravenous one shot administration for 6 days on the average. The results obtained are summarized as follows. 1. Neonates and low birth weight infants were classified into 3 groups by age: 4-7, 8-14, 15-21 day old. Plasma peak levels of CZX were observed at an average of 5 minutes after administration in all 3 groups with mean values of 58.3, 74.9 and 76.9 micrograms/ml, respectively, and the 4-7 day old-group showed a lower value than with other 2 groups. Mean values of AUC were 218.9, 221.0 and 197.0 micrograms.hr/ml, respectively, and no notable difference was observed within each group. Mean values of half-lives of CZX were 3.61, 2.72 and 2.37 hours, respectively, and the younger group tended to have the longer value. 2. Urinary concentrations of CZX ranged 10.9-1.190 micrograms/ml in all of the 3 groups during 0-2, 2-4, 4-6, 6-8 hours after administration. Mean values of urinary recovery rates during 8 hours of the 3 age-groups were 60.1, 68.7, 56.7%, respectively. The oldest group showed the lowest mean value because one of the cases had the lowest value of 34.5% for an unknown reason. 3. Clinical effect of CZX in 16 cases with various bacterial infections and presumptive bacterial infections was evaluated with an efficacy rate of 87.5%. The prophylactic effect was recognized in all 6 cases that were given CZX to prevent infectious diseases. 4. The bacteriological effect was evaluated in only one case with an infection due to Escherichia coli, which was eradicated by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

PubMed1988

[Clinical studies of rokitamycin dry syrup on Chlamydia trachomatis infections in the neonate and infant].

A dry syrup preparation for infants and children of a newly developed 16-membered macrolide antibiotic, rokitamycin, was administered to 5 neonates and low birth weight infants of 6 to 25 days after births at a dose level of 10 mg/kg on an empty stomach then plasma drug levels were determined. The dry syrup preparation was also given to a total of 19 Chlamydia trachomatis infection cases of 7 days to 8 months old neonates, low birth weight infants and infants including 12 cases of pneumonia, 2 cases of conjunctivitis and 5 non-symptomatic carriers at an average daily dose level of 48.1 mg/kg in 2 to 4 doses for an average of 19 days and its clinical effects, bacteriological effectiveness, side effects and effects on laboratory test values were examined. The obtained results are summarized as follows. 1. Because the test subjects were neonates and premature infants, obtainable amounts of blood samples were limited, thus it was not possible to determine time courses of plasma drug levels to reach their peaks. Peak plasma levels, however, were speculated to be similar to those in children. Plasma half-lives of the drug were also not determinable, but they seemed to be somewhat longer than those in children. 2. Clinical efficacies were determinable in the 2 cases of conjunctivitis and 10 of the 12 cases of pneumonia, with excellent or good results in both cases of the former and with excellent or good results in 9 of the 10 determinable cases of the latter. Thus, the overall efficacy rate was high, 91.7%. 3. Bacteriological efficacies were determinable in 18 cases including non-symptomatic carriers. C. trachomatis was eradicated in 16 of the cases with an overall efficacy rate of 88.9%. 4. Diarrhea was observed in 2 cases, which were suspected as side effects of the drug. 5. No abnormalities were observed in the laboratory test results. Judging from the above results, this drug appears to be useful for the treatment of C. trachomatis infections of neonates, low birth weight infants and infants.

Chlamydia Infections↗

PubMed1988

[Clinical studies of rokitamycin dry syrup on skin and soft tissue infections in the pediatric fields].

Rokitamycin (RKM) dry syrup, a newly developed macrolide antibiotic, was administered to children with ages between 6 months and 15 years and 10 months suffering from skin and soft tissue infections including 41 cases of impetigo, one case of staphylococcal scalded skin syndrome (SSSS) and 2 cases of subcutaneous abscess totalling 44 cases. The average daily dose level used was 31.3 mg/kg divided into 3 or 4 doses, for an average of 6 days of treatment. MICs of 4 different macrolide antibiotics including RKM, erythromycin (EM), josamycin (JM) and midecamycin acetate (MDM acetate) were determined against 32 bacterial strains isolated from these cases including 30 strains of Staphylococcus aureus and 2 strains of Streptococcus pyogenes. The inoculum level used was 10(6) cells/ml. Among these strains of bacteria, 20 strains of S. aureus and 1 strain of S. pyogenes were also used, at the same inoculum size, for the determination of MICs of 4 beta-lactam antibiotics including 3 different penicillins such as ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) and cefaclor (CCL), a cephem antibiotic. RKM was then evaluated through the above treatment for its clinical efficacy, bacteriological effects, side effects and effects on laboratory test values. Obtained results are summarized as follows. 1. Activities of drugs tested were compared to each other. MIC90 of RKM against S. aureus averaged 0.39 microgram/ml, and against no strains of S. aureus showed MIC values of higher than 25 micrograms/ml, thus, the antibacterial activity of RKM against S. aureus was the highest among the 8 drugs tested. The activity of MCIPC was next highest followed by that of DMPPC, MIC determination was done on only 2 strains, or, for some drugs, only one strain, of S. pyogenes, and RKM showed activities somewhat lower than ABPC and EM, and similar to JM and CCL within the limited testing. 2. Clinical efficacies of RKM determined by doctors in charge were 97.6% in the 41 cases of impetigo, with good or excellent efficacies were observed, 100% in the single case of SSSS and the 2 cases of subcutaneous abscess. Thus an overall efficacy on the 44 cases was rated very high, at 97.7%. 3. Clinical efficacy rating according to accumulated scores was determinable in 37 cases including all the 3 diseases on the third day of treatment with an efficacy rate of 89.2%. Ratings were determinable on the fifth and the seventh days of treatment in 24 and 21 cases, respectively, with all the cases judged good or excellent.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

PubMed1988

[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)

Adolescent↗