The Japanese Journal of Antibiotics
Online ISSN : 2186-5477
Print ISSN : 0368-2781
ISSN-L : 0368-2781
Volume 42, Issue 6
Displaying 1-17 of 17 articles from this issue
  • ZENZO NAGASAWA, TADATAKA NISHIMURA, FUMIO NAGUMO, HIROSHI UEDA, JUTARO ...
    1989 Volume 42 Issue 6 Pages 1257-1270
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In vitro antibacterial activities of 9 antibiotics including aztreonam (AZT) against clinically isolated Gram-negative bacteria were determined using MIC-2000 plus system. Bacteria were isolated from clinical materials in Saga Medical School during a period from May 1987 to March 1988.
    Summarized results were as follows:
    1. AZT showed excellent antibacterial activities against Escherichia coli, Klebsiella pneumoniae, Proteus sp. and Haemophilus influenzae, and MIC80 values of AZT against these organisms were lower than 0.20μg/ml.
    2. Antibacterial activities of AZT were superior to cephem antibiotics compared against Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii and Serratia marcescens.
    3. The MIC50 and MIC80 of AZT against Pseudomonas aeruginosa were 12.5μg/ml and 25μg/ml, respectively.
    4. AZT did not show any antibacterial activity against Acinetobacter sp. and Xanthomonas maltophilia.
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  • HEIHACHIROU KAWASAKI
    1989 Volume 42 Issue 6 Pages 1271-1278
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Aztreonam (AZT), monocyclic β-lactam antimicrobial agent, was administered to 9 children at a dose level of 30mg/kg through intravenous drip infusion for half-hour.
    Using serum levels of the drug obtained in blood samples, pharmacokinetic parameters were calculated and a simulation curve of serum levels was drawn automatically using a micro-computer.
    The mean values (n=9) for elimination constant (Kel) and half-life (T 1/2) were 0.67 hr-1 and 1.08 hours, respectively.
    The mean apparent volume of distribution was 4.29L, and serum clearance was 0.17L/kg/hr. A basic analysis for the efficacy dose of AZT was performed using above mentioned parameters.
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  • TSUNEKAZU HARUTA, KAN-ETSU OKURA, SHIGEKAZU KUROKI, HATSUMI YAMAMOTO, ...
    1989 Volume 42 Issue 6 Pages 1279-1285
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    The transferability of cefodizime (THR-221, CDZM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus.
    The mean blood concentration was 195±18.3μg/ml using phosphate buffer solution (PBS) standard and 474±22.0μg/ml using rabbit serum standard, respectively, at 15 minutes after intravenous administration of the drug at a dose level of 100mg/kg. The mean concentration in CSF vs. PBS standard was maximum at 60 minutes after administration, and the mean maximum concentration was 8.74±2.16μg/ml.
    Pharmacokinetic parameters calculated from those values were as follows, respectively, for PBS standard and rabbit serum standard; Cmax (CSF/serum): 4.48% and 1.84%. AUC (CSF/serum): 6.15% and 2.02% between 15 and 60 minutes, 10.6% and 3.00% between 15 and 120 minutes and 13.4% and 3.48% between 15 and 180 minutes. T 1/2 for CDZM in CSF: 141 minutes in both cases. T 1/2 (CSF/serum): 3.27 and 2.11.
    Concentrations in CSF determined using an high performance liquid chromatography method in another rabbits were similar to those determined using the bioassay vs. rabbit serum standard.
    The bioassayed concentration of this drug (AUC (CSF/serum)) vs. PBS standard ranked 9th among 23 other β-lactam antibiotics tested.
    That is, the drug distributed favorably as compared to other antibiotics, and it may be worthwhile of running clinical trials on this drug in meningitis when antimicrobial potential against main pathogens of meningitis are considered.
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  • KAN-ETSU OKURA, TSUNEKAZU HARUTA, YUTAKA KOBAYASHI
    1989 Volume 42 Issue 6 Pages 1286-1292
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    A study was done on cefodizime (THR-221, CDZM) in combination with ampicillin (ABPC) for its transferability to cerebrospinal fluid (CSF) of rabbits with experimental meningitis caused by Staphylococcus aureus. Blood and CSF were collected at 15, 30, 45, 60, 90, 120 and 180 minutes after intravenous administration of CDZM at 100mg/kg to 6 rabbits, ABPC at 100mg/kg to 4 rabbits and simultaneous administration of both drugs at 100mg/kg each to 5 rabbits.
    Drug concentrations were assayed with an high performance liquid chromatography method, and pharmacokinetic parameters were calculated.
    The comparison revealed no significant difference in concentrations achieved among different groups.
    Therefore, the mutual transferability of these drugs to CSF was not considered to interact adversely due to the simultaneous administration of both drugs.
    Accordingly, CDZM may be a candidate of chemotherapeutics in the therapy of purulent menigitis, and it is worthy of further investigations.
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  • OSAMU ARIMASU, HIDENORI MEGURO, FUJIAKI HIRUMA, NOBUYUKI SUGIE, TOSHIA ...
    1989 Volume 42 Issue 6 Pages 1293-1305
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Cefodizime (THR-221, CDZM), a new cephalosporin antibiotic, was evaluated for its safety and efficacy in 27 children with various bacterial infections. The episodes of infections included pneumonia (6 cases), bronchopneumonia (11 cases), lung abscess (1 case), acute pharyngitis (2 cases), cervical lymphadenitis (1 case), infected cephalohematoma (1 case), urinary tract infection (1 case), sepsis (2 cases) and purulent meningitis (2 cases). CDZM was effective in all but one, and its efficacy rate was 96. 3%. The main etiologic pathogens were Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Spreptococcus agalactiae, Escherichia coli, Citrobacter freundii and Branhamella catarrhalis. The elimination rate was 92.3%.
    As adverse reactions or abnormalities, diarrhea was encountered in 4 cases. A slight elevation of serum transaminases or eosinophils was observed in 4 cases.
    The serum half-life was approximately 1.8-1.9 hours in children after intravenous bolus injections. Concentrations of CDZM in cerebrospinal fluids were well above MIC values of CDZM against those organisms responsible for the infections.
    The data suggest that CDZM is a safe and effective antibiotic when used in children with bacterial infections including purulent meningitis.
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  • HAJIME SATO, AKIRA NARITA, KIMIKO MATSUMOTO, SHINICHI NAKAZAWA, HIROYU ...
    1989 Volume 42 Issue 6 Pages 1306-1321
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Experimental and clinical study of cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, was done in the field of pediatrics and the results obtained are summarized as follows:
    1. Serum levels and urine excretion were examined after 60-minute drip infusion of CDZM at a dose level of 10mg/kg to 1 patient, at 20mg/kg to 4 and at 40mg/kg to 1. Peak levels in serum were 66.3μg/ml for the 10mg/kg dose occurring 1 hours after the dose, 118.1μg/ml (mean) for 20mg/kg, 259.2μg/ml for 40mg/kg, thus a dose-response was observed.
    T 1/2's (beta phase) were between 1.17 and 1.69 hours. Urinary recovery rates of the drug were between 71.5% and 98.0% in the first 8 hours after administration.
    2. The concentration in the cerebrospinal fluid was 0.76μg/ml and the serum level was 380.67μg/ml at 15 minutes after intravenous administration of 433mg of CDZM to a patient with purulent meningitis.
    3. The clinical efficacy rate was 95.2% in a total of 21 cases, i. e., 1 purulent meningitis, 10 respiratory tract infection, 3 whooping cough, 5 urinary tract infection, 1 purulent infection of soft tissues and 1 acute thyroiditis.
    Diarrhea occurred in 1 case as adverse reactions. Abnormal changes in laboratory test results occurred as 1 case each of slightly elevated GOT·GPT and GOT.
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  • HARUHI NAKAMURA, MITSUNOBU MIYAZU, KEIKO KASAI, NAOICHI IWAI, YOICHI T ...
    1989 Volume 42 Issue 6 Pages 1322-1335
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    1. Absorption and elimination
    Serum and urinary levels of cefodizime (CDZM, THR-221) were determined in 7 children with ages ranging from 3 to 12 years after a intravenous bolus injection of the drug at 20mg/kg. The average serum level of the drug was 119.27±13.83μg/ml at 30 minutes, then decreased gradually with a half-life of 2.01±0.25 hours to 10.56±2.93μg/ml at 6 hours. The average urinary elimination rate was 77.34±12.60%.
    2. Clinical study
    CDZM was given to the following 39 patients with ages ranging from 2 months to 15 years and clinical efficacy, bacteriological response and adverse reactions were evaluated. The treated cases were 2 cases of acute purulent tonsillitis, 30 cases of acute pneumonia, 1 case of acute purulent otitis media and 2 cases of acute urinary tract infections. Clinical efficacies were excellent in 29 cases, good in 5 cases and poor in 1 with an efficacy rate of 97.1%. Organisms presumed to be pathogens included 3 strains of Streptococcus pneumoniae, 1 β-Streptococcus, 1 Staphylococcus epidermidis, 9 Haemophilus influenzae (1 β-lactamase producing strain and 8 nonproducing strains) and 1 Enterococcus faecalis. The last one was decreased and the others were eradicated with an eradication rate of 93.3% for all strains.
    Adverse reactions occurred in no patients. Abnormal changes in laboratory test values involved only 1 case each of elevated GOT, elevated GOT and GPT, eosinophilia and thrombocytosis.
    Based on the above-mentioned result and features of this drug, it was confirmed that this drug showed an excellent usefulness in the treatment of infections in childhood. It may be also effective in the management of infections under immunosuppression.
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  • YOSHIKUNI NAKAO, HIDETOSHI TAKEUCHI, HIROSHI KIMURA, HIDEKI ISHIKAWA, ...
    1989 Volume 42 Issue 6 Pages 1336-1345
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Clinical trials of cefodizime (CDZM, THR-221) were carried out in pediatric infection.
    Results are summarized as follows.
    1. The mean half-life of CDZM in the serum following intravenous injection of CDZM (20mg/kg) was about 2.06 hours.
    2. The mean urinary excretion rate of CDZM within 8 hours after intravenous injection of CDZM was 60.1%.
    3. CDZM was administrated to 19 pediatric patients with various infections; 9 cases of pneumonia, 3 bronchitis, 1 cervical lymphadenitis, 2 tonsillitis and 4 urinary tract infections. The overall efficacy rate was 94.7%.
    4. No adverse reactions were observed. Abnormal laboratory test values found were thrombocytosis in 2, slight elevation of GOT and GPT in 1 and eosinophilia in 1 patient.
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  • YOSHIHIRO KOMADA, SHOUJIRO ARAI, HITOSHI KAMIYA, MINORU SAKURAI, SHIN ...
    1989 Volume 42 Issue 6 Pages 1346-1357
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    In this study, cefodizime (CDZM, THR-221) was administered to 34 children with infections and the efficacy was evaluated in 30 patients. The efficacy rate was 90.0% and CDZM was proved to be a highly effective antibiotic for infectious diseases in childhood. We also demonstrated that CDZM had strong antibacterial activities against both Gram-positive and Gram-negative bacteria. No severe toxicity related to intravenous injection of CDZM was observed in our 34 cases.
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  • YASUHIRO MOCHIZUKI, DAISUKE HATA, HIDEO OHKUBO, AKIRA YOSHIDA, HIROMI ...
    1989 Volume 42 Issue 6 Pages 1358-1365
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Cefodizime (THR-221, CDZM), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 20 children with bacterial infections (Table 1), and the following results were obtained.
    1. CDZM was administered in 3 or 4 divided doses at daily dosages ranging from 54.5 to 84.2mg/kg administered by 30 minutes drip infusion or intravenous injection to 20 patients (7 cases of acute tonsillitis, 6 cases of pneumonia, 2 cases each of bronchitis and suppurative cervical lymphadenitis, and 1 case each of acute pharyngitis, acute enteritis and furunculosis) and the following clinical results were obtained: excellent, 7 cases; good, 11 cases; fair, 2 cases. The overall efficacy rate was 90% (Table 4).
    2. MICs of CDZM against 15 strains of isolated organisms are shown in Table 2. MICs against all 7 strains of Haemophilus influenzae were less than 0.025μg/ml. MIC against 1 out of 5 strains of Streptococcus pneumoniae was 0.05μg/ml and those against 2 strains were 0.10μg/ml and against the other 2 were 0.20μg/ml. MICs against 3 strains of Staphylococcus aureus were 1.56, 25 and higher than 100μg/ml, respectively.
    3. No clinical adverse reaction was observed in any of the 20 patients. Eosinophilia was observed in 2 cases. A slight elevation of S-GOT was found in 1 patient (case No.8) and moderate elevation of S-GOT and S-GPT in another (case No.18)(Table 4). In case No.18, the S-GOT and S-GPT activity improved after the administration of the drug was stopped.
    4. These data suggest that CDZM is a useful new antibiotic in the treatment of children with susceptible bacterial infections and may be used as a first choice antibiotic for the treatment of respiratory tract infection in children.
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  • YOICHI HIRABAYASHI, HIROHIKO HIGASHINO, MINORU KINO, URARA NOBORI, HIT ...
    1989 Volume 42 Issue 6 Pages 1366-1380
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Cefodizime (CDZM, THR-221), a new cephem antibiotic, was investigated for its clinical efficacy and pharmacokinetics in children. The results obtained are summarized as follows.
    1. Antimicrobial activities
    Antimicrobial activities of CDZM against clinically isolated organisms were determined. MICs of CDZM against 1 strain each of Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae were 0.05μg/ml to 0.10μg/ml. Especially, MIC against all 6 strains of Haemophilus influenzae was≤0.024μg/ml. This MIC value was lower than those of other antibiotics such as cefotaxime, cefotiam, cefazolin, piperacillin.
    2. Pharmacokinetics
    CDZM was given to 1 case at a dose of 20mg/kg by a 60-minute intravenous drip infusion. The peak value of serum concentration of CDZM was 207.80μg/ml at the end of the infusion. The half-life was 2.15 hours. The mean urinary excretion rate was 68.5% in the first 4 hours, 79.2% in 6 hours and 76.5% in 8 hours after the 30-minute drip infusion.
    3. Clinical efficacy
    CDZM was given to a total of 27 patients, 13 with pneumonia, 1 with bronchitis, 2 with acute pharyngitis, 1 with purulent tonsillitis, 5 with urinary tract infection, 1 each with retrograde cholangitis, acute enteritis, pericementitis, phlegmon and inguinal lymphadenitis.
    Overall clinical efficacies were excellent in 5 cases, good in 17 and the efficacy rate was 81%.
    Bacteriological effects were investigated in 13 cases and the eradication rate was 85%.
    No adverse reactions were observed in any case.
    As abnormal laboratory findings, elevated GOT, GPT, Al-P, LAP and γ-GTP, were noted in 1 out of the 28 cases examined.
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  • TSUNEKAZU HARUTA, KAN-ETSU OKURA, SHIGEKAZU KUROKI, TADASHI MATSUDA, Y ...
    1989 Volume 42 Issue 6 Pages 1381-1384
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Cefodizime (THR-221, CDZM), a newly developed injectable cephem antibiotic, was injected intravenously to 13 cases of pediatric infections. Patients received the drug at a dose level of approximately 20 mg/kg×3 times daily. The results obtained are summarized as follows.
    1. Clinical efficacy was excellent in 4 patients, good in 6 and poor in 0 for 10 cases (2 phlegmon, 1 periproctal abscess, 5 pneumonia and 2 bronchitis) except 3 Mycoplasma pneumonia.
    2. Three strains of pathogens were followed for their changes (Streptococcus pyogenes in 1 phlegmon, Klebsiella pneumoniae in periproctal abscess and Haemophilus influenzae in 1 bronchitis) and they were found to have been eliminated.
    3. No adverse reactions occurred. Abnormal changes in laboratory test data found were 2 cases of eosinophilia, 1 case each of increased GOT and GPT, and thrombocytosis, but none of them was severe.
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  • ICHIRO YOKOTA, EIJI TAKEDA, YASUHIRO KURODA
    1989 Volume 42 Issue 6 Pages 1385-1390
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Clinical studies were performed on cefodizime (THR-221, CDZM), a new cephem antibiotic as described below.
    CDZM was administered to 13 patients in dose levels ranging from 55 to 96mg/kg/day t. i. d. for 3-7 days (5.5 days on average). These patients included 8 with pneumonia, 2 with tonsillitis, 1 each with bronchitis, phlegmon and urinary tract infection.
    The overall efficacy rate was 92.3%, i. e., emcacy was excellent in 8, good in 4 and poor in 1.
    Bacteriological efficacy was 83.3%, i. e., 5 strains of bacteria (Streptococcus pneumoniae 1, Haemophilus influenzae 3, Haemophilus parainfluenzae 1) were eradicated and 1 was unchanged (Enterobacter cloacae, MIC 100μg/ml).
    Clinical side effect was not observed during the treatment. Laboratory abnormalities were observed in 2 cases, i. e., a slight elevation of GPT and a mild eosinophilia.
    The above results suggest that CDZM is a useful antibiotic for treating pediatric bacterial infections.
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  • TAKANORI SEKIGUCHI, TAKASHI OKAMOTO, KATSUAKI OHARA, HIROKO KOUZAN, MI ...
    1989 Volume 42 Issue 6 Pages 1391-1398
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Cefodizime (CDZM, THR-221) was given intravenously to 20 children with the following acute bacterial infections: 2 cases each of tonsillitis, bronchitis, purulent cervical lymphadenitis, and urinary tract infections and 12 cases of pneumonia. Good clinical responses were obtained in 18 patients out of the 20, and bacteriologically, all of the 5 strains identified were eradicated. No side effect was obtained except one case of eosinophilia.
    From the above clinical results, it is apparent that CDZM is a useful antibiotic for the treatment of pediatric patients with various kinds of bacterial infections.
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  • MASAHARU NIINO, KAICHI KIDA, HIROSHI MATSUDA, MITSUHARU MURASE
    1989 Volume 42 Issue 6 Pages 1400-1413
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Cefodizime (CDZM, THR-221) was evalated for its pharmacokinetics, safety and efficacy in 30 pediatric patients with bacterial infections.
    The following results were obtained.
    1. The pharmacokinetics of CDZM in 6 children were investigated with a dose level of 20mg/kg via intravenous injection. Mean serum half-lives (T 1/2 β) of the drug were 120.9 minutes (HPLC) and 115.6 minutes (bioassay). In 8 hours after administration of CDZM, urinary excretion rates were 74.7% (HPLC) and 75.0% (bioassay).
    2. The clinical efficacies of CDZM were studied in 29 pediatric patients, comprising 22 with respiratory tract infections, 2 with urinary tract infections, 2 with enteritis, 2 with lymphadenitis and 1 with gingivitis. The clinical efficacies were excellent in 13, good in 13 and fair in 3, with an efficacy rate of 89.7%.
    3. The eradication rate for pathogens identified in 7 pediatric patients was 60% (6/10). The clinical efficacy rate in cases where pathogens were identified was 100% in terms of excellent+good evaluations.
    4. Only one case of mild diarrhea was observed as a side effect associated with CDZM. Laboratory tests revealed abnormal value of slightly elevated eosinophil in 3 cases.
    The data suggested that CDZM is a safe and effective injectable antibiotic for the treatment of infections in children.
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  • HIROSHI WAKIGUCHI, TAISUKE OKADA, KAYOKO KAWAI, HIROAKI HISAKAWA, YASU ...
    1989 Volume 42 Issue 6 Pages 1414-1423
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Therapeutic effects of cefodizime (CDZM, THR-221), a new cephalosporin having a methoxyimino group, were examined in various infectious diseases in children.
    Clinical efficacy rates were 100% (3/3) in pneumonia, 100% (5/5) inacute bronchitis, 75% (3/4) in upper respiratory infections and 100% (1/1) in each of a croup and a mixed infection with Streptococcus pyogenes and staphylococcal impetigo. Hence, the overall efficacy rate was 92.9% (13/14).
    Adverse effects were observed in 2 cases, i. e. exanthema provably due to drug allergy in 1 case and a slightly elevated GPT in another.
    Changes in serum concentrations and urinary excretion of CDZM were examined in a child with no infection. T 1/2 values obtained were 124.5 minutes (bioassay) and 143.4 minutes (high performance liquid chromatography (HPLC)). Eight hour recovery rates in urine were 62.9% (bioassay) and 65.4% (HPLC).
    CDZM was considered to be a safe and useful drug in treating various infectious diseases in children.
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  • MASAHIRO YANAGISHIMA, MASANORI YANAI, TADAMICHI YANAGI, YOSHIRO TSUJI, ...
    1989 Volume 42 Issue 6 Pages 1424-1435
    Published: June 25, 1989
    Released on J-STAGE: May 17, 2013
    JOURNAL FREE ACCESS
    Laboratory and clinical studies on cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, were done. The results obtained are summarized as follows:
    1. Absorption and elimination were examined in a total of 5 cases including a case of 10mg/kg intravenous drip infusion for 30 minutes, 2 cases of 20mg/kg rapid intravenous injection and 2 cases of 40mg/kg drip infusion for 30 minutes. Maximum serum levels were attained immediately after drip infusion or rapid injection. Cmax's were 119.2μg/ml for 10mg/kg, 374.9μg/ml or 255.7μg/ml for 20mg/kg, and 321.3μg/ml or 431.8;g/ml for 40mg/kg. These values were determined using an high performance liquid chromatography (HPLC) method. In general, values using the bioassay were higher than those with the HPLC method. T 1/2 (β)'s were between 1.74 and 1.93 hours using HPLC, and between 1.77 and 2.24 hours using bioassay. Urinary recovery rates were examined in 3 out of 5 cases.
    Cumulative urinary recovery rates were57.9-90.6% with HPLC method and 50.4-88.0% with bioassay in a period of 0-8 hours after administration.
    2. Clinical efficacy was evaluated in a total of 22 cases including 14 cases of respiratory tract infections, 5 cases of urinary tract infections and 3 cases of cellulitis. Clinical efficacy rate was 95.2%. Bacteriologically, pathogenic organisms were eradicated in 90.0%. As adverse reactions, 1 angular stomatitis, 1 diarrhea and 1 loose stool were noted. Abnormal laboratory test values detected were 1 case of increased GPT and 1 case of increased GOT and GPT.
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