Clinical Analysis of Voriconazole Concentrations in Cerebrospinal Fluid and Blood in Patients with Ryptococcal Meningitis

  Objective  To investigate the concentrations of voriconazole (VCZ) in the central nervous system (CNS) of patients with cryptococcal meningitis and the relationship thereof.

  Methods  We retrospectively analyzed the trough concentration of VCZ in the cerebrospinal fluid (CSF) and the blood of 25 adult patients who had cryptococcal meningitis, and who were not infected with HIV. We also examined patient-level characteristics that could contribute to the differences in CSF/plasma VCZ concentration ratio.

  Results   The trough concentration of VCZ in plasma ranged from 0.38 to 8.56 mg/L, and the median (P₂₅, P₇₅) was 1.81 (1.40, 3.84) mg/L. The trough concentration of VCZ in CSF ranged from 0.17 to 3.92 mg/L, and the median (P₂₅, P₇₅) was 1.02 (0.54, 1.84) mg/L. The CSF VCZ trough concentration showed a slight negative correlation with the nucleated cell counts in CSF, but the correlation was not statistically significant (r=−0.377, P=0.063). There was a positive correlation between VCZ concentrations in CSF and that in the plasma (r=0.736, P<0.001), and the median (P₂₅, P₇₅) CSF/plasma ratio was 0.43 (0.34, 0.68). The CSF/plasma ratio did not statistically correlate with age, body surface area (BSA), radiology changes (hydrocephalus), or intracranial pressure.

  Conclusion  There is a positive correlation between VCZ concentration in CSF and VCZ concentration in the plasma, and no influencing factors of CSF/plasma ratio were found.