Biomedical subjects

T Motohiro

Publications and source records attributed to T Motohiro.

At least 37 records · Page 2Linked to original sources

PubMed1994

[Basic and clinical studies on cefditoren pivoxil in pediatric field].

Cefditoren pivoxil (CDTR-PI, ME1207) granules, a new oral cephem, was given to pediatric patients with infectious diseases to evaluate antibacterial activities against clinical isolates, pharmacokinetics, clinical efficacy and safety, and the following results were obtained. 1. In sensitivity test, 30 strains were used comprised of 5 species, isolated from the patients before administered with CDTR-PI. Against Staphylococcus aureus, MICs of 7 agents, cefditoren (CDTR), cefaclor, cefixime, cefteram, cefotiam, cefpodoxime and methicillin, were determined. Against other 4 species, MICs of the above 6 agents excluding methicillin were determined. Among Gram-positive cocci tested, the MICs of CDTR were 0.78 to 100 micrograms/ml or higher against S. aureus (16 strains), < or = 0.025 microgram/ml against Streptococcus pyogenes (5 strains), and 0.10 or 0.39 microgram/ml against Streptococcus pneumoniae (2 strains). These values were equal to or lower than those of conventional cephems and of methicillin. Among Gram-negative rods tested, the MICs of CDTR were < or = 0.025 microgram/ml against Haemophilus influenzae (3 strains), and 0.10 or 0.20 microgram/ml against Escherichia coli (4 strains). Also, these values were equal to or lower than those of conventional cephems. 2. When CDTR-PI granules was orally administered in a single dose of 3.0 mg/kg to 1 patient and that of 6.0 mg/kg to 2 patients 30 minutes after meal, plasma CDTR concentrations reached their maxima 4 hours after administration in the former patient and 1 or 2 hours after administration in the latter 2 patients, and the peak plasma concentrations were 1.91, 3.46 and 4.82 micrograms/ml with half-lives of 1.01, 0.81 and 0.88 hours and AUCs of 8.62, 9.89 and 13.52 micrograms.hr/ml, respectively. Dose-dependency was observed for the peak plasma concentrations and AUCs also tended to depend on dose excepting for the AUC in one 6.0 mg/kg patient. 3. The urinary concentrations in the above patients reached their peaks at 4 to 6 hours after administration in one 3.0 mg/kg patient and at 4 to 6 hours and 2 to 4 hours after administration in two 6.0 mg/kg patients, and the corresponding values were 126.0, 195.0 and 234.0 micrograms/ml, respectively. Recovery rates in the first 8 hours after administration were 18.2, 24.6 and 21.3%, respectively. 4. Of 53 patients with 13 diseases, CDTR-PI was clinically judged "excellent" in 32 (60.4%) and "good" in 21 (39.6%), showing excellent efficacy. 5. Bacteriologically, excellent results were obtained, i.e., 29 (96.7%) of 30 strains from 5 species were eradicated. 6. Side effects were observed in none of the 54 patients treated.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1993

Primary structure of scombrine gamma, protamine isolated from spotted mackerel (Scomber australasicus).

Spotted mackerel protamine, scombrine, was isolated from the sperm of a spotted mackerel (Scomber australasicus) by extraction with sulfuric acid and fractionated into one major (scombrine II) and one minor (scombrine I) components by chromatography on CM-Sephadex C-25. Scombrine II gave a single band, whereas scombrine I gave three bands upon PAGE. Scombrine II (scombrine gamma) consists of 34 amino acid residues, and its sequence is: Pro-Arg-Arg-Arg-Arg-Arg-Ala-Ser-Arg-Pro-Val-Arg-Arg-Arg-Arg-Arg- Ala-Arg-Arg-Ser-Thr-Ala-Val-Arg-Arg-Arg-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg. The ion spray mass spectrum shows that scombrine gamma has a molecular mass of 4,532.13 Da. The other minor component (scombrine I) is considered to be a mixture of degradation products of scombrine gamma based on the results of PAGE and ion spray mass spectrometry. Scombrine gamma has a similar sequence to sardaine Z2 from striped bonito except for two positions.

Amino Acid Sequence↗

PubMed1993

[Basic and clinical studies on S-1108 in pediatric field].

S-1108 is a new oral esterified cephem antibiotic. Its active form, S-1006, has a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Furthermore, S-1006 is extremely stable against beta-lactamases with some exceptions. In the present study, we conducted laboratory and clinical evaluations of S-1108 granules in pediatrics. The obtained results are summarized as follows. 1. A drug sensitivity test revealed that MIC80 of the drug against 456 clinical isolates of Staphylococcus aureus that had been kept in our laboratory was 6.25 micrograms/ml, similar to those of cefaclor (CCL) and methicillin (DMPPC). The most frequent MIC was 1.56 micrograms/ml against 20 strains of S. aureus isolated from patients who received this drug, and this value was similar to those for CCL, amoxicillin (AMPC) and DMPPC. As regards to Streptococcus pyogenes, MIC of S-1006 was < or = 0.025 microgram/ml against 449 clinical isolates in our culture collection and 7 strains obtained from patients who received this drug, and these MICs are similar to those of cefteram (CFTM). MICs of S-1006 against 5 strains of Streptococcus pneumoniae obtained from patients who received this drug were < or = 0.025 microgram/ml, 0.10 microgram/ml or 0.39 microgram/ml which are similar to those of CFTM. MICs of S-1006 against 4 strains of Haemophilus influenzae obtained from patients who received this drug were 0.05 or 0.10 microgram/ml which are similar to those of CFTM. 2. When S-1108 granule preparation was administered to 1 patient at 4.0 mg/kg, the peak plasma concentration of S-1006 was 1.25 microgram/ml. S-1108 granule preparation was also administered to 2 patients at 6.0 mg/kg, and the peak plasma concentrations were 2.43 micrograms/ml and 2.23 micrograms/ml. Plasma half-lives were 1.11 hours after 4.0 mg/kg and 1.28 hours in both patients given 6.0 micrograms/ml. AUCs were 4.06, 8.37 and 7.73 micrograms.hr/ml, respectively. A dose-response relationship was observed between the two doses. 3. Urinary concentration was the highest during the 4-6-hour period for a patient given 4.0 mg/kg, and during the 0-2-hour or 4-6-hour period for 2 patients given 6.0 mg/kg. The peak concentrations were 258.0, 602.0 and 500.0 micrograms/ml, respectively, and urinary recovery rates during the 0-8-hour period were 38.9, 38.3 and 23.1%, respectively. 4. Clinical effects were excellent or good in 88 of 93 patients, showing a very high efficacy rate of 94.6%.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1993

[Laboratory and clinical studies on flomoxef in neonates and premature infants].

Flomoxef (FMOX), an oxacephem antibiotic of beta-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40 mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5 mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0- to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40 mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20 mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7 micrograms/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161 micrograms.hr/ml. The same dose (20 mg/kg) of FMOX was administered to 3 premature infants of 5- 16- and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9 micrograms/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201 micrograms.hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40 mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0 micrograms/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357 micrograms.hr/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

PubMed1992

Primary structures of sardaines Z1 and Z2, protamines isolated from striped bonito (Sarda orientalis).

Striped bonito protamine, sardaine, was isolated from the sperm of striped bonito (Sarda orientalis) by extraction with sulfuric acid followed by ion-exchange chromatography. The preparation gave a single band upon polyacrylamide gel electrophoresis. Sardaine consists of 34 amino acid residues, and its sequence is: Pro-Arg-Arg-Arg-Arg-Arg-Ser(Ala)-Ser-Arg-Pro-Val-Arg-Arg-Arg-Arg-Arg-Tyr -Arg- Arg-Ser-Thr-Ala-Ala-Arg-Arg-Arg-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg. At position 7, serine (sardaine Z1) is partially replaced by alanine (sardaine Z2). The ion spray mass spectrum shows that sardaines Z1 and Z2 have molecular masses of 4,612.49 and 4,596.09 Da, respectively. The sequence of sardaine Z1 is 100% identical with that of thynnine Z2 from tuna fish (both fish belong to Scombridae, Perciformes).

Amino Acid Sequence↗

PubMed1992

Wilson's disease treatment by triethylene tetramine dihydrochloride (trientine, 2HCl): long-term observations.

Wilson's disease is an autosomal recessive disorder characterized by an accumulation of a toxic amount of copper in the body. Triethylene tetramine dihydrochloride (trientine, 2HCl) is a new chelating agent that may be effective in the removal of excess copper but long-term efficacy has not yet been investigated. Here we report the use of trientine over more than 8 years in 2 patients with Wilson's disease who could not tolerate D-penicillamine. We found no significant side effect, except a decreased serum iron concentration without clinical symptoms of anemia. In annual examinations at a steady state, the serum copper levels remained below 20 micrograms/100 ml. The 24-hour urinary copper excretion was less than that found using D-penicillamine, while the basal copper excretion, after 5 days abstinence from trientine, was maintained below 100 micrograms/day. Both hepatic and neurological manifestations except bulbar symptoms were recovered without any initial deterioration.

Adolescent↗

PubMed1992

[Clinical studies on cefprozil granules in pediatric skin soft tissues infections].

Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1992

[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)

Administration, Oral↗

PubMed1992

[Basic and clinical study of meropenem in pediatric field].

Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1992

[Pharmacokinetics and clinical effects of cefdinir 10% fine granules in pediatrics].

Cefdinir (CFDN), a newly developed oral cephalosporin in a 10% fine granular form, was administered to 8 children and concentrations of the drug in plasma and urine and urinary recovery rates of the drug were determined. The subjects were divided into 2 groups of 4 children each; one group received 3 mg/kg of CFDN at 1 hour before meal (in the fasting state), and the other, at 30 minutes after meal. To study clinical and bacteriological effects of this drug, a mean dose of 4.8 mg/kg t.i.d. was administered for 8 days on the average to 9 children with various infections; tonsillitis (3 cases), acute bronchitis (1), pneumonia (1), acute purulent otitis media (1), urinary tract infection (2), and impetigo (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin, amoxicillin (AMPC) against 4 strains freshly isolated from children receiving CFDN. An inoculum size of 10(6) cfu/ml was used in the MIC-determinations. Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these children. The results obtained are summarized as follows. 1. Mean plasma peak levels of CFDN were observed at 2 hours after administration in the before-meal group and 4 or 5 hours after administration in the after-meal group mean peak values of 0.88 and 0.50 micrograms/ml, respectively. Mean half-lives were 1.61 hours in the before-meal group and 2.54 hours in the after-meal group, and mean AUCs were 4.24 in the former and 3.59 micrograms.hr/ml in the latter. 2. Mean urinary peak concentrations of CFDN were observed during 2-4 hours after dosing in the before-meal group and during 6-8 hours in the after-meal group with values of 93.3 and 44.8 micrograms/ml, respectively, in cases for which plasma concentrations of drugs were determined. Mean urinary recovery rates during the first 8 hours after administration in the before- and after-meal groups were 16.6 and 13.4%, respectively. 3. Good clinical effects were obtained with an efficacy rate of 100% in 9 patients with 6 diseases due to bacterial infections. 4. Good bacteriological effects were also obtained against 2 strains of Streptococcus pyogenes, 2 strains of Escherichia coli and 1 strain of Haemophilus influenzae with an eradication rate of 100%. In 3 cases of these and another case (normal flora), strains present before the study were replaced by other strains.(ABSTRACT TRUNCATED AT 400 WORDS)

Amoxicillin↗

PubMed1991

[Alpha-hemolytic streptococcal septicemia and meningitis in immunocompromised children].

Many kinds of microorganisms can produce toxic septicemia in immunocompromised hosts. We are reporting alpha-hemolytic streptococcal septicemia and meningitis in two children with hematological malignancies. [Case 1] 6 year old girl who had been suffering from acute lymphocytic leukemia. She had sepsis and bacterial meningitis in maintenance-therapy for leukemia. Streptococcus sanguis was isolated from the blood and cerebrospinal fluid (CSF). [Case 2] 11 year old girl who had had malignant lymphoma (non-Hodgkin type). She also had sepsis and bacterial meningitis due to Streptococcus mitis which was isolated from blood and CSF in maintenance-therapy. Both cases had been treated with anti-cancer drugs and had severe granulocytopenia. Positive rate of blood cultures during the recent 6 years (1984.1-1989.12) at our department was 6.0% (total number of cultures were 2,019, positive cultures were 121). Strains of 131 bacteria were determined; Gram-positive cocci were 70 strains (53.4%) and Gram-negative rods were 52 strains (39.7%). Fifteen strains (11.5%) of alpha-hemolytic Streptococci were isolated during 6 years. One hundred thirteen cases of septicemia were analysed in medical charts and 12 cases of alpha-hemolytic streptococcal septicemia were observed (5 cases with infective endocarditis and 7 cases in immunocompromised states).

Child↗

PubMed1991

[Severe infections due to Streptococcus milleri in children].

Streptococcus milleri (S. milleri) is found in healthy individuals in the mouth, nasopharynx, throat, vagina and in feces, and has been reported to be isolated from several infectious diseases in man, particularly from abscess in various parts of the body. We report two cases of severe infections due to S. milleri isolated from subdural abscess and pleural empyema. [Case 1] 13 year old boy who had been healthy until he was noticed to have meningeal signs and was diagnosed as left subdural abscess with siagonantritis by cranial CT scans. S. milleri was isolated from subdural abscess and maxillary sinus. [Case 2] 10 year old boy who had encephalitis and severe mental retardation after measles at 6 months of age. He had a fever, dyspnea and chest X-ray abnormalities and was diagnosed as right pleural empyema. Three strains of organism, S milleri, Bacteroides spp. and Fusobacterium nucleatum were isolated from the pleural effusion.

Adolescent↗

PubMed1990

[Pharmacokinetics and clinical effects of cefdinir 5% fine granules in pediatrics].

Cefdinir (CFDN), a newly developed oral cephalosporin in 5% fine granular form, was administered to 10 boys at 1 hour before meal (in the fasting state) and concentrations of the drug in plasma and urine and its urinary recovery rates were determined. The subjects were divided into 2 groups of 5 boys each; one group received 3 mg/kg of CFDN, and the other, 6 mg/kg. To 6 of the 10 children the drug was administered in the two different dose levels using the cross-over method. To study clinical and bacteriological effects of this drug, a mean dose of 4.6 mg/kg t.i.d. was administered for 8 days on the average to 40 children with various infections; pharyngitis (4 cases), tonsillitis (2), acute bronchitis (2), pneumonia (8), scarlet fever (6), acute purulent otitis media (1), urinary tract infection (12), impetigo (2), phlegmon (1), lymphadenitis (1) and subcutaneous abscess (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin (MCIPC), amoxicillin (AMPC) against 13 strains of 6 species freshly isolated from children receiving CFDN. An inoculum size of 10(6) cfu/ml was used in the MIC-determinations. Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these patients. The results obtained are summarized as follows. 1. Mean plasma peak levels of CFDN were observed at 3 hours after administration in both the 3 mg/kg and 6 mg/kg groups with mean peak values of 0.68 and 1.35 micrograms/ml, respectively. Mean half-lives were 2.06 hours in the 3 mg/kg group and 1.61 hours in the 6 mg/kg group, and mean AUCs were 3.5 in the former and 6.5 micrograms.hr/ml in the latter. Thus, dose-response between the 2 doses was observed in plasma levels and AUCs. 2. To 3 patients, CFDN was given in the two different doses using the cross-over method. Mean plasma peak levels of CFDN were 0.71 and 1.31 micrograms/ml in the doses of 3 mg/kg and 6 mg/kg, respectively. Half-lives were 1.39-2.90 hours in the 3 mg/kg group and 1.21-1.48 hours in the 6 mg/kg group, with AUCs of 3.4-3.7 and 4.1-7.5 micrograms.hr/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1990

[Evaluation of effectiveness of rokitamycin dry syrup in acute enteritis in pediatrics. A comparative study on rokitamycin and fosfomycin dry syrups].

Because Campylobacter jejuni is most frequently identified as a causative organism of bacterial enteritis in pediatrics, a study was done to evaluate the clinical efficacy against Campylobacter enteritis and the safety of a macrolide antibiotic, rokitamycin (RKM). In case of acute enteritis, RKM was used in a form of dry syrup at a dose level of approximately 30 mg (in potency)/kg body weight and its efficacy and safety were compared to those of fosfomycin (FOM) dry syrup which is currently in use at a dose level of 60 mg (in potency)/kg. Both drugs were administered, as a rule, in 3 divided daily dose (RKM before meal and FOM after meal) for 5 consecutive days. Comparisons of the drugs were made using a well-controlled method. Obtained results are summarized as follows. 1. No significant differences in background factors of the 2 drug groups were apparent, hence it was deemed that no obstacles existed in making comparative studies of the 2 groups with regard to their efficacies and safeties. 2. Overall efficacy rate against Campylobacter enteritis was 100% in the RKM group with a rate of excellent efficacy of 91.3% and the former was 94.4% in the FOM group with the latter of 72.2%. Though the RKM group apparently showed higher rates by 5.6% and 19.1%, respectively, for overall and excellent efficacies, they were not statistically significant as both drugs showed good efficacies. When acute cases of enteritis other than those caused by Campylobacter were included in the analysis, overall efficacy rates and rates of excellent efficacy were, respectively, 97.6% and 85.7% for the RKM group and 88.6% and 68.2% for the FOM group, thus RKM showed higher efficacy rates by 9.0% and 17.5%, respectively. These differences were deemed statistically significant using the U-test. 3. Numbers of days required for most of the major symptoms to subside were 3 days or less for the group for which RKM was used against Campylobacter enteritis. Similar results were observed for the FOM group also. In cases of acute enteritis due to other causes than Campylobacter, slower recoveries were observed for both the RKM and the FOM groups than in Campylobacter enteritis cases, with the latter group slower than the former. In cases of puruloid stool, the recovery in the RKM group was significantly faster by U-test than the FOM group, and a similar trend was observed overall. 4. Bacteriologically, the eradication rate of Campylobacter in the RKM group was very good at 91.3% with the FOM group showing a rate of 78.9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

PubMed1990

[Experimental and clinical studies on cefodizime in pediatrics].

Cefodizime (CDZM), a newly developed injectable cephem antibiotic, was given via bolus intravenous injection at each of 3 dose levels of 10, 20 and 40 mg/kg to each 3 children, and serum and urinary levels and urinary recovery rates were followed. A total of 57 patients received CDZM in the following regimen via bolus intravenous injection, and clinical efficacies, and microbial responses were evaluated. Mean dosage per application: 20.9 mg/kg, number of application per day: between 2 and 4 (2 times for 3 patients, 3 for 26 patients and 4 for 28 patients), mean duration of the therapy: 1 week. Patients consisted of 1 case of peritonsillar abscess, 2 acute bronchitis, 38 pneumonia, 8 urinary tract infection, 1 staphylococcal scalded skin syndrome, 2 cellulitis, 4 purulent lymphadenitis and 1 typhoid fever. In addition to the patients mentioned above 6 patients who dropped out were involved in the evaluation of adverse reactions and influence of the drug on laboratory test data, and the following results were obtained. 1. Five minutes after bolus intravenous injection in doses of 10, 20 and 40 mg/kg, serum levels determined by the bioassay method were at their maxima, i.e. 114.0, 264.6 and 461.6 micrograms/ml, respectively. Serum levels of drugs were dose-dependent throughout all the dosage levels tested. Mean serum half-lives of the drug were 1.757, 1.552 and 1.668 hours, respectively, for the 3 dose levels. Serum levels of the drug determined by the HPLC method were similar to those by the bioassay method: The maximum serum levels occurred at 5 minutes after administration, mean maximum concentrations were 105.5, 264.0 and 461.7 micrograms/ml for the 3 dose levels, and a dose response was noted for the 3 dose levels. The half-lives were 1.755, 1.598 and 1.668 hours, respectively. 2. Mean maximum concentrations in urine determined by bioassay for 2 of 3 cases received 10 mg/kg and 3 cases each given 20 and 40 mg/kg of CDZM were 884.3, 3,061 and 7,352 micrograms/ml, respectively, in the first 2 hours after administration. These levels were also dose-dependent. Mean recovery rates were 74.4, 78.4 and 71.5%, respectively, in the first 8 hours after administration. Mean maximum concentrations in urine measured by HPLC were similar to those determined by bioassay, i.e. 962.3, 3,404 and 7,899 micrograms/ml in the first 2 hours. They were, also, dose-dependent. Mean recovery rates were 82.1, 86.0 and 76.5%, respectively, in the first 8 hours after administration. The HPLC determinations gave slightly higher levels than the bioassay.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1990

[Pharmacokinetics and clinical studies of norfloxacin in the pediatric field].

Norfloxacin (NFLX) tablets with a potency of 50 mg/tablet or 100 mg/tablet were administered at doses of 1 to 4 tablets (1.5 to 6.1 mg/kg) orally 30 minutes before meals to 12 children with ages ranging from 8 years 9 months to 12 years 5 months, and serum/urinary NFLX levels and urinary recovery rates were determined. The drug sensitivity tests for NFLX and 10 other drugs were conducted against 128 strains of Shigella sonnei (10(6) CFU/ml) which had been isolated from pediatric patients with bacillary dysentery. In order to evaluate clinical and bacteriological effects of NFLX and its safety in the pediatric field, NFLX 50 mg tablets were administered t.i.d. (mean 8.3 mg/kg) for 5 days to 42 pediatric patients with bacillary dysentery. Similarly, this drug was administered in b.i.d. or t.i.d. (mean 6.7 mg/kg) for 4 days to 4 pediatric patients with urinary tract infections. The following results were obtained: 1. According to the dosage, the subjects were divided into 3 groups with dose levels 1.5-2.8 mg/kg, 3.1-4.7 mg/kg and 5.2-6.1 mg/kg. These groups had 5, 2 and 5 subjects, respectively. Mean serum drug concentrations for the 3 dosage groups were at peak levels of 0.27, 0.64 and 1.51 micrograms/ml at 4, 2 and 1 hour(s) after administration, respectively. Pharmacokinetic parameters for these dosage groups were as follows: Tmax values were 3.0, 3.0 and 1.2 hours; Cmax values were 0.32, 0.78 and 1.56 micrograms/ml; serum half-lives were 2.2, 2.4 and 2.3 hours; and AUCs were 1.65, 3.98 and 6.06 micrograms.hr/ml, respectively. Thus, dose-dependent responses were observed among the 3 dosage groups. 2. Mean peak urinary drug concentrations for the 3 dosage groups were 45.8, 109.2 and 215.1 micrograms/ml, respectively, and the peaks appeared 2-4 hours after administration. Mean recovery rates up to 8 hours after administration were 18.3%, 24.5% and 28.7%, respectively for the 3 dosages. 3. In a drug sensitivity test against 128 strains of S. sonnei, the most frequent MIC value of NFLX was 0.78 micrograms/ml against 65 strains, followed by 0.39 micrograms/ml for 56 strains. Together, these strains accounted for 94.5% of the strains tested. No resistant strain to this drug was observed and the antibacterial activity of this drug was second only to colistin, similar to that of ofloxacin, better than those of enoxacin and seven other drugs. 4. Clinical efficacy rate of NFLX against bacillary dysentery was 95.2% in 21 cases in which the evaluation was possible.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1990

[Influence of cefodizime via intravenous bolus injection on human fecal flora].

Cefodizime (CDZM), a newly developed injectable cephem antibiotic, was given to 8 healthy male volunteers with ages 23-28 years (mean: 24 years) and body weights 54-73 kg (mean: 64 kg). 4 volunteers received 2 g b.i.d., intravenous infusion for 5 days, and 4 volunteers had 4 g b.i.d. for the same duration. We studied changes in bacterial flora and drug levels in feces, as well as changes in susceptibility of isolated microbes to CDZM, cefmetazole, cefotaxime (CTX) and cefoperazone. Adverse drug reactions and changes in laboratory findings were also investigated. The following results were obtained. 1. In fecal flora for the 2 g b.i.d. group, on day 3 of treatment Enterobacteriaceae were identified in only 2 of the 4 cases. Individual microbe counts decreased or fell below detection limit (10(2) cells/g) on day 3 of treatment. Colony forming units (CFUs) of Enterobacteriaceae on day 5 of treatment were similar to those on day 3. After the end of treatment, its CFUs increased. The mean CFU of Enterobacteriaceae on day 10 after the end of treatment increased to about the same level as before dosing. However, some microbes did not revert to pretreatment levels. Of other Gram-negative bacilli, Pseudomonas sp. increased in one case transiently on day 3 of treatment. After day 3 of treatment, its CFU decreased. Gram-positive microbes showed various changes. Mean CFU of yeast like organism (YLO) increased between day 3 of treatment and day 3 after the end of treatment and its mean CFU decreased on day 10 after the treatment. As for anaerobes, CFUs of Bacteroides fragilis group organisms and overall anaerobes showed no distinctive changes. Clostridium difficile were detected in two cases. In one case, C. difficile was noted at levels between 1.1 X 10(3) cells/g and 2.0 X 10(6) cells/g at the following sampling times: days 1 and 3 of treatment and days 3, 5, 10 and 20 after the end of treatment. In other case, it was noted at levels of 1.8 X 10(5) cells/g on day 20 after the end of treatment. D-1 toxin was detected in one case before dosing, and in three cases (the concentration of D-1 toxin was 250 ng/g or 500 ng/g) on day after treatment. Enterobacteriaceae in fecal flora of 4 cases given 4 g b.i.d. frequently decreased or fell below detection limit on days 3 and 5 of treatment and day 3 after the end of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1990

[Pharmacokinetics of BMY-28100 in multiple administration].

A multiple dose trial of BMY-28100, a new oral cephalosporin, was performed in volunteers, in order to evaluate its safety and pharmacokinetics. BMY-28100 was administered orally 250 mg t.i.d. for 7 days to seven healthy adult males. No side effects nor abnormal laboratory findings were observed. Peak levels of serum concentration and half-lives after the first and 19th administrations were 4.45 and 4.83 micrograms/ml and 1.3 and 1.1 hours, respectively. Urinary recoveries in 24 hours were 53.4% on day 1 and 56.2% on day 7. There was no tendency towards accumulation in blood upon continuous daily dosing of 250 mg t.i.d.

Administration, Oral↗