[Transferability of cefodizime to cerebrospinal fluid of rabbits with meningitis caused by Staphylococcus aureus].
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 +/- 18.3 micrograms/ml using phosphate buffer solution (PBS) standard and 474 +/- 22.0 micrograms/ml using rabbit serum standard, respectively, at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF vs. PBS standard was maximum at 60 minutes after administration, and the mean maximum concentration was 8.74 +/- 2.16 micrograms/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 beta-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.
Haruta
T
T
Department of Pediatrics, Kobe City General Hospital.
Okura
K
K
Kuroki
S
S
Yamamoto
H
H
Kobayashi
Y
Y
D000818:Animals; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000209:etiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000134:cerebrospinal fluid
D002439:Cefotaxime; C033356:cefodizime