4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety.

Abstract

In a recent randomized, double-blind, placebo-controlled crossover trial, we demonstrated efficacy of 4-aminopyridine (4-AP) in improving disability of patients with multiple sclerosis (MS). Here we describe the relationship between dosage, serum level, efficacy, and safety of intravenously and orally administered 4-AP in the same group of 70 MS patients. After both intravenous and oral administration there was a significant 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 times a day showed a large variation and fluctuation in serum levels. After 12 weeks of oral treatment (maximum daily dosage 0.5 mg/kg body weight), a statistically significant improvement was found for the smooth pursuit gain of the eye movements (estimated effect 0.14, 95% confidence interval 0.06-0.23, p < 0.001). The amount of improvement was significantly related to 4-AP serum levels (p = 0.0013). Side effects after intravenous 4-AP occurred frequently and were very troublesome (pain in infusion arm, dizziness). Side effects during oral treatment (dizziness, paresthesias) were very mild and occurred 30-45 min after intake of the medication and could be related to high serum levels.

• Authors: H A Van Diemen, C H Polman, J C Koetsier, A C Van Loenen, J J Nauta, F W Bertelsmann
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) Vol. 16 Issue 3 Pg. 195-204 (Jun 1993) ISSN: 0362-5664 [Print] United States
• PMID: 8504436 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• 4-Aminopyridine

Topics

• 4-Aminopyridine (administration & dosage, adverse effects, blood)
• Administration, Oral
• Adult
• Aged
• Double-Blind Method
• Female
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Multiple Sclerosis (drug therapy)
• Pursuit, Smooth (drug effects)