Chiral synthesis of the BC-ring system of ciguatoxin from D-glucose.
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Ciguatera Poisoning↗
Biomedical subjects
H Meguro
Publications and source records attributed to H Meguro.
[A case of supramediastinal neurinoma: its operative approach (via supraclavicular route) and radiographic findings (target sign)].
A 76-year-old female with supramediastinal tumor was admitted. CT scan showed central high density area surrounded by low density area and MR imaging emphasized the same concentric circle. This concentric circle pattern on CT scan and MR imaging is called "Target sign", which is known as characteristic radiographic finding of neurinoma. Therefore we could diagnose her case as mediastinal neurinoma preoperatively. She underwent operation through the supraclavicular approach and the tumor was completely resected. By incising the skin through the modified left hemi-collar incisional line and cutting the clavicula at its central part, we could ensure a good operative field and safely performed this operation without mid-sternotomy or thoracotomy. The supraclavicular approach for the operation of supramediastinal tumor is useful.
Aged↗
[Clinical evaluation of faropenem against infections in pediatric fields].
The recent increases in the prevalence of penicillin-resistant Streptococcus pneumoniae becomes a point at issue clinically. We carried out a clinical study in 40 cases in the pediatrics department, as faropenem (FRPM) was proved to have an excellent antimicrobial activity against penicillin-resistant Streptococcus pneumoniae. The study was planned to investigate in detail the movement of stools that had been a problem in a clinical development studies out before. In this study, an observation of the daily movement of stools was one of the principal evaluation items, hence the patients were divided into two groups. One group (S-group) were administered FRPM only, the other group (E-group) were administered FRPM in combination with a medicine for intestinal disorders (Enteronon-R). An observed frequencies of any loose bowel movements were 94.7% in S-group, and 63.2% in E-group, hence the study suggested that the combination drug was effective. The patients observed higher frequencies of development of the movement of stools, all of them were recovered from in the course of administration or within 4 days after administration, however whether or not being treated symptomatic therapy. Clinical efficacy rates of FRPM on mainly respiratory infections were 94.6%. In this study, 4 strains (patients) of penicillin-resistant Streptococcus pneumoniae were isolated. Against penicillin-resistant Streptococcus pneumoniae, FRPM demonstrated more potent antibacterial activity than the oral penicillins and cephems tested here except cefditoren. Clinical efficacies was deemed effective in all of the 4 cases, and bacteriologically, 3 organisms were eradicated. As for side effects including diarrhea and loose stool, no serious side effects were observed. Based on the above results, FRPM is effective against most infections in the pediatric field which Streptococcus pneumoniae are isolated at high frequencies highly, and is considered to cases in be useful an attention will have to be paid to stool movement, however.
Adolescent↗
[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates].
The efficacy, safety and pharmacokinetics of cefozopran (CZOP) were evaluated in neonates and the following results were obtained: 1. Of the 12 patients treated with CZOP, judgment of clinical efficacy was evaluable in 10 patients (including 5 with pneumonia and 3 with urinary tract infections). The treatment was effective and the causative organism was eradicated in 100% of the patients. 2. No adverse signs and symptoms were recognized during the treatment with CZOP. A slight elevation of direct bilirubin was recognized as an abnormal alteration of laboratory test values in one patient. The value, however, returned to the normal range after the completion of treatment. 3. The pharmacokinetic evaluation was made in 3 of the 12 patients. The blood CZOP levels were recognized in proportion with the dosages. The elimination half lives (T 1/2) in those patients were 8.92, 2.90 and 2.76 hours. Prolongation of T 1/2 was recognized in the patient aged 0 day. It was possible to examine the urinary excretion only in one patient aged 18 days. The excretion rate of the drug was 68.6% of dose by 8 hours after administration. These results suggest that CZOP is a drug useful for treatment of infections in neonates as well, with high efficacy and safety.
Bacterial Infections↗
[Clinical evaluation of a new macrolide antibiotic, azithromycin, in the pediatric field].
Azithromycin (AZM) preparations in fine granules and capsules were evaluated in 36 pediatric patients with various infections. In patients with pneumonia caused by Moraxella catarrhalis, Haemophilus influenzae or Mycoplasma pneumoniae, bronchitis, pharyngitis, scarlet fever, whooping cough, or campylobacter enteritis, AZM was found effective in 94.4% (34/36). As for the bacteriological efficacy of AZM, all of 12 strains identified were found eradicated by the treatment. Plasma T 1/2(24 approximately 48 hrs.) of AZM in fine granules, given two patients at 10 mg/kg body weight once daily for 3 days, were 41.5 and 51.4 hours, while AUC0 approximately infinity was 7.45 and 13.44 mg.hr/ml. The rates of AZM recovered in the urine samples from two pediatrics patients in the first 81 hours of treatment, when it is given in fine granules at 10 mg/kg body weight once daily for 3 days, were 6.27% and 11.0%. Data from 43 patients were included for drug safety evaluation. Neither adverse reactions nor abnormal laboratory changes were observed. In conclusion, AZM was found useful in treatment of pediatric infections.
Anti-Bacterial Agents↗
[Pharmacokinetic and clinical studies with cefluprenam in the pediatric field. Pediatric Study Group of Gefluprenam].
Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals. Informed consents from legal representatives were obtained prior to the study. 1. Clinical efficacy. Two-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases. However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease. In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1%. As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections. The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable beta-lactams. On 32 cases with S. pneumoniae infection, the efficacy rate of CFLP was 100.0%. In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8%. In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276). Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia. As for bacteriological responses, eradication rates were 95.2% (177/186) in total. Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae. Against Gram-negative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis. In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases. In these cases, the eradication rate was 98.1% (52/53). 2. Pharmacokinetics. CFLP was intravenously administerrd to 12 subjects at doses of 20 to 40 mg (potency)/kg. In 9 subjects aged more than 12 months, maximum serum levels (Cmax), T 1/2 beta and AUC of CFLP were 155.3 +/- 9.8 micrograms/ml, 1.43 +/- 0.18 hours and 111.7 +/- 15.0 micrograms.hr/ml, respectively, when a dose of 20 mg (potency)/kg was used. In 2 subjects aged not more than 12 months, the mean Cmax, T 1/2 beta and AUC were 153 micrograms/ml, 1.6 hour and 81 micrograms.hr/ml, respectively, at a dose of 20 mg(potency)/kg. The mean Cmax, T 1/2 beta and AUC were 332 micrograms/ml, 0.93 hours and 157.3 micrograms.hr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg. In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413 +/- 512, 1471 +/- 524, and 470 +/- 115 micrograms/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary excretion rate of 61.4 +/- 6.3%. In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770 micrograms/ml in 0-2 p3d 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1%. Cerebrospinal fluid concentrations of CFLP, on 10 subjects with purulent meningitis dosed 40-103 mg (potency)/kg were 3.2-32.9 micrograms/ml at 0.5-2 hours after administration within 4 days after the onset of
Bacteria↗
Fluorimetric determination of diarrhetic shellfish toxins in scallops and mussels by high-performance liquid chromatography.
The fluorimetric determination of okadaic acid (OA) and dinophysistoxin-1 (DTX-1), the principal toxins of diarrhetic poisoning, is reported. The digestive glands of mussels or scallops were homogenized with 2-propanol. OA and DTX-1 were extracted from the homogenate, with hexane-ethyl acetate and labelled with 2,3-(anthracenedicarboximido)ethyl trifluoromethanesulfonate in dry acetonitrile. After cleaning up by passage through a short silica gel column, the fluorescent derivatives were determined by HPLC. The derivatives were at first separated on a Develosil Ph-5 column, and only the target fraction obtained was introduced into a Develosil ODS K-5 column by a valve-switching device. Both toxins were determined in the range 2.5-500 pg, and the detection limits were 0.8 pg (OA) and 1.3 pg (DTX-1) with a signal-to-noise ratio of 3.
Animals↗
[Optimum dose study of cefozopran in the pediatric field].
Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.
Bacterial Infections↗
[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates and premature infants. A study of cefozopran in the perinatal co-research group].
The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.
Bacterial Infections↗
Pharmacokinetics and clinical effects of cefozopran in pediatric patients.
An investigation was made into pharmacokinetics and clinical effects of the newly-developed cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), in pediatric patients. In 26 patients in whom pharmacokinetics were investigated, peak serum concentrations of CZOP administered at doses of 10, 20 and 40 mg/kg by i.v. injection were 21.3 +/- 10.0 (mean +/- standard deviation), 51.0 +/- 9.9 and 68.3 +/- 0.7 micrograms/ml, respectively. Serum concentrations at 6 hours after administration were 2.9 +/- 1.7, 2.3 +/- 0.9 and 4.6 +/- 2.6 micrograms/ml, with the levels roughly above MIC90s for dominating pathogenic bacteria being maintained until 6 hours after treatment. Urine concentrations were in the range between 200 and 560 micrograms/ml at 4 to 6 hours after dosing. Cumulative urine excretion accounted for 70 to 80% of dose. In 11 patients in whom pharmacokinetic investigations were performed, peak serum concentrations of CZOP administered at doses of 10, 20 and 40 mg/kg by 30-min. i. v. drip infusion were 37.1, 66.3 +/- 25.5 and 95.7 +/- 8.9 micrograms/ml, respectively. Serum concentrations at 6 hours after dosing were 1.6, 2.3 +/- 0.8 and 3.0 +/- 0.4 micrograms/ml, respectively, with the levels above MIC90s for dominating pathogenic bacteria also being maintained until 6 hours after administration. Urine concentrations were 190 micrograms/ml or more until 8 hours after dosing and the cumulative urinary excretion accounted for 50 to 70% of dose. In 9 patients with meningitis in whom CZOP penetration into cerebrospinal fluid was investigated, concentrations in the fluid of the compound i.v. injected at doses from 40 to 53 mg/kg were in the range between 1.6 and 43.4 micrograms/ml exceeding MICs for pathogenic bacteria at 1 to 1.5 hours after dosing. In all of the 38 patients in whom pharmacokinetic investigations and clinical evaluations were performed, CZOP was good to excellent (excellent in 22 patients and good in 16 patients). Also in bacteriological evaluations, all of the 31 strains of investigated pathogenic bacteria were eradicated. The clinical efficacy rates for the 335 subjects for clinical evaluations were 97.0% (195/201) for patients in whom pathogenic bacteria were detected (group A), and 95.5% (128/134) for patients in whom no pathogenic bacteria were detected (group B). In bacteriological evaluations, the eradication rates of Gram-positive and Gram-negative bacteria were 96.3% (77/80) and 94.5% (155/164), respectively, with the eradication rate in total being 95.1% (232/244). Safety investigations were performed in 364 patients. Adverse reactions were reported in 11 patients (3.0%), including diarrhea (aqueous stool and soft stool) in 7 patients (1.9%) and drug rash (rash, eruption and wheal) in 4 patients (1.1%). Abnormal laboratory test values were noted in 54 patients, including eosinophilia in 20 patients (6.3%) and elevated GPT in 20 patients (6.3%). The adverse reactions and abnormal laboratory test values were not serious, disappearing or improving during the continued treatment period or as a result of discontinuation of the treatment. Serum and urine concentrations of CZOP, when administered by i.v. injection and 30-min, i.v. drip infusion at doses of 10, 20 and 40 mg/kg, were higher than the MICs for pathogenic bacteria until 6 hours after dosing. The drug also showed favorable penetration into cerebrospinal fluid. It was therefore considered that CZOP was a highly useful drug for the treatment of pediatric infections with sufficient bacteriological and clinical efficacy when administered at a dose of 40 to 80 mg/kg three to four times daily.
Bacteria↗
Automatic determination of hydroperoxides of phosphatidylcholine and phosphatidylethanolamine in human plasma.
An automatic method for the determination of hydroperoxides of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is reported. Sample plasma was deproteinized with a fourfold volume of methanol. After centrifugation, the supernatant was injected directly into an HPLC system without further treatment. The hydroperoxides of PC and PE were concentrated and washed on an ODS column followed by introduction into two analytical columns, a silica gel and an aminopropylsilica gel column, which were connected in series, by column switching. After the separation, they were detected by postcolumn detection with diphenyl-1-pyrenylphosphine. The compounds were determined at picomole levels within 30 min with good reproducibilities. By using only a silica gel column as an analytical column, PC hydroperoxides were determined within 20 min, and samples could be injected into it at 15-min intervals. Those methods made it possible to inject a sample of up to 2 ml at one time and up to 8 ml by repeated injections and to determine phospholipid hydroperoxides in human plasma at picomole levels.
Chromatography, High Pressure Liquid↗
[Pharmacokinetic and clinical studies with azithromycin (fine granule) in the pediatric field. Pediatric Study Group of Azithromycin].
Azithromycin (AZM) in 10% fine granules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.5% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition AZM concentrations were determined in blood samples from 18 patients and in urine samples from 17 patients to examine o pharmacokinetic characteristics of AZM. 1. Absorption and excretion: Cmax's in 16 patients who received 10 mg/kg and 2 patients who received 20 mg/kg were 0.29 +/- 0.24 micrograms/ml and 0.75 micrograms/ml, respectively, while T 1/2's were 42.0 +/- 11.8 hours for the former and 51.3 hours for the latter. AUC(0 to approximately infinity)'s were 10.72 +/- 5.00 micrograms x hr/ml in the former and 28.83 micrograms x hr/ml in the latter. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 10 mg/kg AZM in 14 patients, while it peaked at 24 to 48 hours in the patients who received 20 mg/kg. Urinary recovery rates in the first 120 hours after the start were 9.1 +/- 2.6% for 10 mg/kg and 10.8 +/- 3.4% for 20mg/kg. 2. Clinical efficacy: The study received 619 entries and 564 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate, combining both "Excellent" and "Good" cases was 94.3% in 246 cases where pathogens were identified, classified as Group A. The efficacy rate was 90.7% for the remaining 321 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 92.2%. For the 116 cases where the patients had failed to respond to previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 94.0%. 3. Adverse reactions and abnormal laboratory tests: Incidents of diarrhea, soft stool, skin rashes, or vomiting were found in 15 patients (2.5%) of 596 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 15 patients including 4 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 23 patients (5.6%), increase in eosinophils in 28 (7.1%), increase in platelet count in 2 (0.5%), decrease in platelet count in 1 (0.3%), elevation of GOT in 3 (0.8%), and elevation of GPT in 6 (1.6%).(ABSTRACT TRUNCATED AT 400 WORDS)
Absorption↗
[Pharmacokinetic and clinical studies with azithromycin (capsule) in the pediatric field. Pediatric Study Group of Azithromycin].
Azithromycin (AZM) in 100 mg capsules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.9% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition, AZM concentrations were determined in blood samples from 9 patients and in urine samples from 12 patients to examine pharmacokinetic characteristics of AZM. 1. Absorption and excretion: Cmax was 0.45 +/- 0.28 micrograms/ml, T 1/2 was 52.7 +/- 20.2 hours, and AUC(0 approximately to infinity) was 12.09 +/- 4.93 micrograms.hr/ml in the 9 patients each of whom received 8.5 to 14.3 mg/kg AZM. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 8.5 to 14.7 mg/kg AZM in 12 patients and the average urinary recovery rate in 120 hours was 7.3 +/- 2.8%. 2. Clinical efficacy: The study received 139 entries and 119 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate combining both "Excellent" and "Good" cases, was 100% for 40 cases in which pathogens were identified, classified as Group A. The efficacy rate was 97.5% for the remaining 79 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 98.3%. For the 31 cases where the patients had failed to respond to the previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 93.5%. 3. Adverse reactions and abnormal laboratory tests: 8 incidents of diarrhea, skin rashes, urticaria, or vomiting were found in 7 patients (5.4%) of 130 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 7 patients including 2 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 10 patients (9.3%), an increase in eosinophils in 12 (11.4%), an increase in platelet count in 1 (1.0%), an elevation of GOT in 3 (3.1%), an elevation of GPT in 6 (6.2%), and an elevation of LDH in 1 (1.1%). The abnormalities were transient and did not require particular intervention. Moreover, none of the patients indicated clinical signs associated with the abnormal changes of laboratory tests.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
[Pharmacokinetic and clinical studies of S-1108 in the pediatric field. Pediatric Study Group of S-1108].
S-1108 in granules, a new oral cephem antibiotic, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained. 1. Pharmacokinetics S-1108 was administered at single doses of 2, 3, 4, 6 mg/kg orally and the following results were obtained on Cmax, T 1/2 and AUC, respectively: Cmax: 0.79, 1.03, 1.39, 1.06 micrograms/ml, T 1/2: 1.28 +/- 0.40, 1.27 +/- 0.65, 1.10 +/- 0.29, 1.83 hrs., AUC: 2.65 +/- 0.63, 3.99 +/- 2.77, 5.25 +/- 1.83, 5.15 micrograms.hr/ml. These values indicated a dose-dependent pharmacokinetic behavior. Urinary recovery rates were 12.5-30.0% in the first 8(6) hours after administration. 2. Clinical results The clinical efficacy of S-1108 was evaluated in 456 patients with various infections. S-1108 was administered at a dose of 2-4 mg/kg three time a day to most patients. The overall clinical efficacy rate was 95.0%. In 294 cases with identified causative pathogen, the clinical efficacy rate was 96.9%, and the bacteriological eradication rate was 89.0%. Side effects occurred in 18 (3.23%) of 558 patients subjected to safety analyses. The main side effect was diarrhea but those side effects were mild and reversible. Abnormal laboratory test results were observed in 25 cases, (eosinophilia and elevated GOT and GPT). These abnormalities were not dose-dependent and also seen with other cephems to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, S-1108 is considered to be very useful at a standard dose of 2-4 mg/kg t.i.d. against most infections encountered in the pediatric field out-patient clinic.
Administration, Oral↗
[Clinical evaluation of a new oral penem, SY5555, in the pediatric field].
A new oral penem antibiotic, SY5555, was evaluated for its safety and efficacy in 35 children with various bacterial infections. SY5555 was effective in 100% of scarlet fever, pharyngotonsillitis, pneumonia, otitis media, bacterial diarrhea, urinary tract infections and skin and soft tissue infections. The etiologic bacteria were eradicated except Salmonella sp. Side effects were observed in 3.5% cases; one was diarrhea and Candida dermatitis, one was loose stool, and one was Candida dermatitis. From these data, SY5555 is thought to be a safe and effective antibiotic in the pediatric field. Regular dose of suspension preparation is 15 mg/kg/day in 3 divided dosages, and when needed the dose may be doubled.
Administration, Oral↗
[Prevalence of penicillin-insensitive Streptococcus pneumoniae and its response to oral beta lactam antibiotics at a primary pediatric office].
Penicillin (PC) resistance of Streptococcus pneumoniae was tested by oxacillin disk method (Bauer-Kirby method) of the strains collected at the primary pediatric office. The rate of oxacillin resistance of S. pneumoniae was 36.4% in 1990, 41.4% in 1991, and 51.9% in 1992, respectively. The efficacy of oral antibiotics in the treatment of PC-insensitive S. pneumoniae infections was also studied retrospectively in 234 cases. Treatment failure rate was 17.7% in the amoxicillin group, 8.7% in the cefpodoxime proxetil group, while it was 42.9% in the cefixime group. These differences were statistically significant. From these data prevalence of PC-insensitive S. pneumoniae is very high in Japanese children, and amoxicillin and cefpodoxime proxetil can be used for the treatment of outpatients with PC-insensitive S. pneumoniae infections.
Administration, Oral↗
[Clinical studies on clarithromycin dry syrup in the pediatric field. Pediatric Study Group of TE-031 Dry Syrup].
Clarithromycin dry syrup, a new drug preparation, was clinically evaluated in the pediatric field and the following results were obtained: 1. Absorption and excretion In infants administered with single oral dose of 5 mg (potency)/kg and 10 mg/kg, the Cmax was 2.26 +/- 0.42 and 3.23 micrograms/ml; Tmax, 1.6 +/- 0.1 and 2.0 hours; T 1/2, 3.89 +/- 0.52 and 2.06 hours; AUC (0-infinity), 13.48 +/- 1.93 and 13.84 micrograms.hr/ml, respectively. Urinary concentrations peaked in 2-4 hours after administration at 5 mg/kg and 0-2 hours at 10 mg/kg. Urinary recovery rates in the first 6 hours were 25.8 +/- 3.9% at 5 mg/kg and 20.7% at 10 mg/kg. 2. Clinical results The clinical efficacy of the drug was evaluated in 150 patients with various infections. Clarithromycin dry syrup was administered to all the patients at daily doses of 10-15 mg/kg divided into 2-3 equal doses. The overall clinical efficacy rate was 98.0%, and this drug was effective in 98.9% of 90 patients for whom the causative pathogens were identified and in 96.7% of the other 60 patients for whom the causative pathogens were unknown. The bacteriological eradication rate was 88.5%. The efficacy and eradication rates for 19 patients who had not responded to previous chemotherapy that lasted for more than three days were 94.7% (18/19) and 75.0%, respectively. Side effects occurred in 4 (2.4%) of 169 patients subjected to safety analyses, but none was serious. As to abnormal laboratory test results, moderate increases of eosinophils and elevations of transaminases were observed in 5.9% of the cases. No particular and serious problems were associated with administration of this drug. Based on the above results, clarithromycin dry syrup is considered to be very useful and have a good compliance at a daily dose of 10-15 mg/kg divided into 2-3 doses.
Administration, Oral↗
[Clinical evaluation of cefozopran in the pediatric field].
A new parenteral cephem, cefozopran (CZOP), was evaluated for its safety and efficacy in 21 children with acute infections. A mild side effect or an abnormality in laboratory tests was observed in one case each, but the safety of CZOP was otherwise observed. CZOP was effective in all of the 18 bacterial infections tested including pneumonia, cellulitis and urinary tract infections, and all the causative organisms were eradicated. Serum half-lives of CZOP were 1.5-1.8 hours and the urinary excretion rates were 63-96% in the first 5-8 hours after administration. These data suggest that CZOP is safe and effective in children with susceptible bacterial infections.
Acute Disease↗