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[Transfer of fosfomycin into the cerebrospinal fluid]
Abstract:
After the fosfomycin (FOM) infusion, its levels in serum and cerebrospinal fluid (CSF) were repeatedly measured in 8 cases without meningitis. 1. The peak concentration of FOM in CSF was 15.5 micrograms/ml with the average of 10.3 micrograms/ml and was reached at 240 minutes with the average of 210 minutes after the infusion. The biological half life time of FOM in CSF was 2 to 6.5 hours. 2. The peak concentration in CSF was compared with it in serum. The average ratio was 4.3 per cent. Each area under the curve (AUC) of FOM concentration in CSF and serum was calculated and average of their ratio was 9.0 per cent. 3. In a case with middle cerebral artery aneurysm, FOM transferred into CSF with ease. The lowest diffusion into the CSF was shown in 2 cases of meningioma. In 3 cases of hypertensive intracerebral hemorrhage with intraventricular perforation, FOM moderately transferred into CSF.
Insights
Fosfomycin (FOM) effectively penetrates the cerebrospinal fluid (CSF) in patients without meningitis, reaching therapeutic levels. Its penetration varies based on neurological conditions, impacting treatment strategies.
Area of Science:
- Pharmacokinetics
- Neuroscience
Context:
- Assessing drug delivery to the central nervous system is crucial for effective treatment.
- Understanding cerebrospinal fluid (CSF) penetration of antibiotics is vital for managing infections and other neurological conditions.
Purpose:
- To quantify the penetration of fosfomycin (FOM) into the cerebrospinal fluid (CSF) in patients without meningitis.
- To determine the pharmacokinetic profile of FOM in CSF, including peak concentration, time to peak, and half-life.
- To compare FOM concentrations in CSF relative to serum and evaluate its transfer across the blood-brain barrier in various neurological conditions.
Summary:
- Fosfomycin (FOM) demonstrated significant penetration into the CSF, with an average peak concentration of 10.3 mcg/ml, reached around 210 minutes post-infusion.
- The biological half-life of FOM in CSF ranged from 2 to 6.5 hours.
- CSF FOM levels averaged 4.3% of serum peak concentrations, and the area under the curve (AUC) ratio was 9.0%, indicating moderate CNS penetration.
- FOM transfer into CSF was notably high in a case of middle cerebral artery aneurysm, low in meningioma cases, and moderate in patients with hypertensive intracerebral hemorrhage with intraventricular perforation.
Impact:
- These findings provide valuable pharmacokinetic data for fosfomycin (FOM) in the central nervous system (CNS) of non-meningitis patients.
- The study highlights the influence of specific neurological conditions on FOM's ability to cross the blood-brain barrier.
- Results can inform clinical decisions regarding the use of FOM for CNS infections or other conditions requiring CSF drug penetration.