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[Transferability of cefpirome to cerebrospinal fluid of rabbits with meningitis caused by Staphylococcus aureus]
Abstract:
The transferability of cefpirome (HR810, CPR) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 362 +/- 6.63 micrograms/ml at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 60 minutes after administration, and the mean maximum concentration was 14.6 +/- 2.85 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows, Cmax (CSF/serum): 4.04%; AUC (CSF/serum): 5.14% between 15 and 60 minutes, 8.12% between 15 and 120 minutes and 10.4% between 15 and 180 minutes; T 1/2 for CPR in CSF: 154 minutes; T 1/2 (CSF/serum): 3.96. In comparison to those of other beta-lactam antibiotics which were obtained in the same way, the transferability of CPR was intermediate, but the peak CSF level was high, and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for this drug.
Insights
Cefpirome (CPR) shows intermediate transferability to cerebrospinal fluid (CSF) in rabbits with Staphylococcus aureus meningitis. Despite this, high peak CSF concentrations suggest potential clinical efficacy for meningitis treatment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Bacterial meningitis remains a significant cause of morbidity and mortality.
- Effective antibiotic penetration into the cerebrospinal fluid (CSF) is crucial for treatment success.
- Cefpirome (CPR) is a cephalosporin antibiotic with broad-spectrum activity.
Purpose of the Study:
- To evaluate the transferability of cefpirome (CPR) into the CSF in a rabbit model of Staphylococcus aureus meningitis.
- To determine pharmacokinetic parameters of CPR in serum and CSF.
- To assess the potential clinical utility of CPR for meningitis treatment.
Main Methods:
- Experimental meningitis was induced in rabbits using Staphylococcus aureus.
- Intravenous administration of cefpirome (100 mg/kg).
- Measurement of cefpirome concentrations in serum and CSF over time.
- Calculation of pharmacokinetic parameters including Cmax, AUC, and T 1/2.
Main Results:
- Mean peak serum concentration of CPR was 362 µg/ml at 15 minutes post-administration.
- Mean peak CSF concentration of CPR was 14.6 µg/ml at 60 minutes.
- CSF/serum ratios for Cmax and AUC indicated intermediate transferability.
- The elimination half-life (T 1/2) of CPR in CSF was 154 minutes.
Conclusions:
- Cefpirome exhibits intermediate penetration into the CSF in this meningitis model.
- The drug achieves high peak concentrations in the CSF.
- Given its antimicrobial potency, further clinical trials are warranted to evaluate cefpirome for meningitis treatment.