Article

OBJECTIVE: To determine if cyclosporine-A-mediated inhibition of p-glycoprotein would increase methylprednisolone entry into the central nervous system thereby permitting a reduction in the systemic methylprednisolone dose. SETTING: Department of Anesthesiology, University of Washington, Seattle, USA. METHODS: Microdialysis probes were used to obtain cerebrospinal fluid and gluteal muscle extracellular fluid samples for measurement of methylprednisolone concentration in pigs. At time zero, a methylprednisolone bolus was given and an infusion started. At 210 min, after reaching a stable methylprednisolone concentration, a cyclosporine-A bolus was given (either 10 or 30 mg/kg) and microdialysis samples collected until 420 min. Plasma samples were collected at 10, 30 min and then every 30 min until the study's end. RESULTS: Cyclosporine-A bolus produced a dose-dependant increase in methylprednisolone concentration in plasma, muscle and cerebrospinal fluid. Importantly, the magnitude of the increase in cerebrospinal fluid was significantly greater than the increase in plasma and muscle. CONCLUSIONS: The relatively greater increase in cerebrospinal fluid concentrations of methylprednisolone is consistent with increased penetration of the blood-brain barrier secondary to cyclosporine-mediated p-glycoprotein inhibition. Theoretically, increased methylprednisolone entry into the central nervous system should allow a reduction in the systemic methylprednisolone dose and a consequent decrease in glucocorticoid-mediated side effects.

Langue : ANGLAIS