Prednisolone Transfer into Cerebrospinal Fluid in Neurological Patients with Continuous Extraventricular Drainage

Prednisolone의 뇌척수액내로의 침투에 대한 약동학적 연구

Background: Corticosteroids have been used to control seizures due to brain tumors, to decrease cerebral edema from a variety of causes, and to prevent inflammatory complications of meningitis. Despite this broad spectrum of use in neurological and neurosurgical disorders, little is known about the correlation between dose and drug concentrations of plasma and CSF in patients with CNS disorder. Thus we examined the prednisolone penetration into CSF in patients with CNS disorder, who were under continuous extraventricular drainage (EVD) to reduce increased intracranial pressure(IICP). Methods : The penetration of systemically administered prednisolone into CSF were evaluated in five neurosurgical patients undergoing EVD. Blood and CSF samples were serially collected up to 12 hours after i.v. administration of prednisolone disodium phosphate(1 mg/kg) over 5 min. Results : Plasma concentrations of prednisolone showed multiphasic decay after i.v. administration of prednisolone. CSF concentration slowly increased to reach peak at 1 to 2 hours after administration. The terminal decay of prednisolone level in CSF was parallel to that in plasma. The mean free fraction of CSF prednisolone was about 0.5 and did not show concentration-dependence as that shown in plasma. In four neurosurgical patients who did not show any evidence of intracranial hemorrhage, the AUC ratio (CSF/plasma) of total prednisolone was $0.15{\pm}0.09$, which indicates that CSF prednisolone concentrations are much lower than unbound plasma concentrations even under the pathologic conditions of brain. However, the AUC ratio of unbound prednisolone $(0.35{\pm}0.19)$ was greater than that of total prednisolone due to the lower CSF protein binding. Conclusion : This low permeability of prednisolone into CSF might support the high dose prednisolone therapy for various pathologic conditions of CNS. For further mechanistic understanding of prednisolone therapy, simultanaous measurement of pharmacodynamic parameters like ICP or CSF production rate together with CSF predinsolone levels seems to be future task.