4-AMINOPYRIDINE IN PATIENTS WITH MULTIPLE-SCLEROSIS - DOSAGE AND SERUM LEVEL RELATED TO EFFICACY AND SAFETY

In a recent randomized, double-blind, placebo-controlled crossover tri al, we demonstrated efficacy of 4-aminopyridine (4-AP) in improving di sability of patients with multiple sclerosis (MS). Here we describe th e relationship between dosage, serum level, efficacy, and safety of in travenously and orally administered 4-AP in the same group of 70 MS pa tients. After both intravenous and oral administration there was a sig nificant relationship between serum levels and 4-AP doses used (p < 0. 001 and p < 0.01, respectively). The use of 4-AP in oral doses three t imes a day showed a large variation and fluctuation in serum levels. A fter 12 weeks of oral treatment (maximum daily dosage 0.5 mg/kg body w eight), a statistically significant improvement was found for the smoo th pursuit gain of the eye movements (estimated effect 0.14, 95% confi dence interval 0.06-0.23, p < 0.001). The amount of improvement was si gnificantly related to 4-AP serum levels (p = 0.0013). Side effects af ter intravenous 4-AP occurred frequently and were very troublesome (pa in in infusion arm, dizziness). Side effects during oral treatment (di zziness, paresthesias) were very mild and occurred 30-45 min after int ake of the medication and could be related to high serum levels.