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Meningeal penetration of apalcillin in man
Abstract:
We have used high performance liquid chromatography to evaluate the meningeal penetration of apalcillin. In subjects without meningitis the penetration was poor and the levels obtained did not exceed 1.75 mg/l. In cases of meningitis, when the spinal fluid albumin level was greater than 0.60 g/l, the levels varied from 5 to 30 mg/l. These figures are in accord with those obtained in cases of experimental meningitis. A dosage of 200 mg/kg/day should allow the treatment of meningitis due to sensitive bacteria and in particular due to Pseudomonas aeruginosa.
Insights
Apalcillin shows poor meningeal penetration in non-meningitis patients but achieves therapeutic levels in meningitis cases. A dosage of 200 mg/kg/day may treat meningitis caused by susceptible bacteria, including Pseudomonas aeruginosa.
Area of Science:
- Pharmacokinetics
- Infectious Diseases
- Neuroscience
Background:
- Apalcillin is an antibiotic.
- Meningeal penetration of antibiotics is crucial for treating meningitis.
- Previous data on apalcillin's CSF penetration is limited.
Purpose of the Study:
- To evaluate the meningeal penetration of apalcillin in patients with and without meningitis.
- To determine if apalcillin levels in cerebrospinal fluid (CSF) are sufficient for treating bacterial meningitis.
Main Methods:
- High-performance liquid chromatography (HPLC) was used to measure apalcillin concentrations.
- Apalcillin levels were assessed in serum and CSF of patients.
- Patient groups included those without meningitis and those with confirmed meningitis.
Main Results:
- In subjects without meningitis, apalcillin penetration was poor, with levels not exceeding 1.75 mg/l.
- In meningitis patients with CSF albumin > 0.60 g/l, apalcillin levels ranged from 5 to 30 mg/l.
- These results align with findings from experimental meningitis models.
Conclusions:
- Apalcillin demonstrates significant meningeal penetration in the presence of meningitis, particularly when CSF albumin is elevated.
- A dosage of 200 mg/kg/day is proposed as potentially effective for treating meningitis caused by susceptible bacteria, including Pseudomonas aeruginosa.