Methylprednisolone infusion during acute exacerbation of MS: plasma and CSF concentrations

Plasma and CSF concentrations of methylprednisolone (MP), after a high-dose intravenous administration (1,500 mg) prescribed to patients presenting acute exacerbation of multiple sclerosis, were measured. A plasma pharmacokinetic study with 1 CSF sample was performed in 9 patients and 4 other patients had a single plasma sample at the time of lumbar puncture. MP plasma kinetics were similar between patients. Pharmacokinetic parameters were very close to previous published values obtained in normal volunteers or patients with rheumatoid disease. Passage of MP into the CSF was delayed since mean plasma/CSF ratio dropped dramatically from 150 at the 2nd h to 25 at the 3rd h after starting infusion. CSF concentrations of MP were high with a mean reaching 522 micrograms/l at the 6th h. The high levels of CSF concentrations suggest that MP may have powerful pharmacological effects within the CNS. No correlation was found between CSF concentration and the clinical response to steroid therapy. The issues related to previous data on clinical, biological and radiological effects of high-dose intravenous MP are discussed in the light of our results.