EXPERIMENTAL STUDIES ON THE PASSAGE OF CEFAMANDOLE SODIUM INTO THE CEREBROSPINAL FLUID

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  • Cefamandole sodiumの髄液中移行に関する実験的研究
  • Cefamandole sodium ノ ズイエキチュウ イコウ ニ カンスル

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Abstract

Passage of cefamandole sodium, a new cephalosporin, into the CSF was studied in experimental staphylococcal meningitis in rabbits, and the following results were obtained.<BR>1) Blood concentrations, CSF concentrations and CSF/serum ratios after an intravenous injection of 100 mg/kg were as follows (an average of the results obtained in 5 rabbits); 30 minutes 198μg/ml, 5.4μg/ml and 2.7%; 1 hour 81.2μg/ml, 4.7μg/ml and 5.8%; 90 minutes 28.9μg/ml, 2.9μg/ml and 10.0%; 2 hours 6.6μg/ml, 1.6μg/ml and 24.2%. These CSF concentrations were almost comparable to those of other cephalosporins, but because of higher blood concentration of cefamandole sodium, CSF/serum ratios were lower at 30 and 60 minutes, respectively.<BR>2) Based on the concentrations in blood and CSF obtained in other 6 rabbits at 15-minute interval following an intravenous injection of 100 mg/kg, half-life (T 1/2) and area under the curve (AUC) were calculated. Peak CSF concentration was attained at 30 minutes after injection, i. e., 22.65μg/ml, and T 1/2 of blood concentration 23.2 minutes, T 1/2 of CSF concentration 28.6 minutes and T 1/2 of CSF/serum ratio 1.23, respectively. AUC CSF/serum ratio percentage was 13.6% (15-60 minutes), 13.5% (15-90minutes), 13.7% (15-120 minutes) and 14.0% (15-150 minutes), and no increase was noted with the lapse of time.<BR>3) These results suggested that the passage of cefamandole sodium into the CSF is relatively good but the disappearance of the drug from the CSF is rapid.<BR>4) In order to obtain a therapeutic success in the treatment of bacterial meningitis, maintenance of a closer contact of the causative organism with the drug for a certain period of time is considered to be important, although an effective CSF concentration is a prerequisite. Consequently, when evaluating the effectiveness of an antibiotic in the treatment of bacterial meningitis, the determination of T 1/2 of CSF concentration is an important requirement. Considereration of T 1/2 will be required in the dosage of the antibiotic.<BR>5) When Haemophilus influenzae meningitis is going to be treated with cefamandole sodium, it should be injected intravenously 50 mg/kg 8 times daily in order to secure a definite clinical response. However, further studies will be necessary, including the problem of adverse reactions.

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