title: Pharmacokinetics and safety of 3,4-diaminopyridine base in healthy Japanese volunteers.
abstract: OBJECTIVE
  3,4-diaminopyridine (3,4-DAP) is commonly used for treating neuromuscular diseases, such as the Lambert-Eaton myasthenic syndrome, but the pharmacokinetics of 3,4-DAP base have not been investigated. We therefore studied 3,4-DAP base pharmacokinetics in healthy Japanese volunteers.
  
  
  METHODS
  In this crossover study, we administered a single oral dose of 10 or 20 mg 3,4-DAP base to healthy Japanese volunteers (n = 5) after food intake, or 10 mg 3,4-DAP to fasting individuals. We measured serum 3,4-DAP concentrations, performed electrocardiography (ECG), and administered questionnaires.
  
  
  RESULTS
  After administration of 10 or 20 mg 3,4-DAP following food intake, the maximum serum concentrations (Cmax) were 8.09 ± 4.47 ng/mL and 35.8 ± 15.7 ng/mL, respectively (mean ± standard deviation; SD), and the areas under the serum concentration-time curve (extrapolated to infinity) were 639 ± 213 ng x min/mL and 2,097 ± 936 ng x min/mL (mean ± SD), respectively. Administration to fasted individuals indicated that food intake did not significantly alter 3,4-DAP pharmacokinetics. ECG showed no clinically significant changes, but PR intervals were prolonged in all cases. Two out of 5 subjects showed perioral paresthesia symptoms after administration of 20 mg 3,4-DAP.
  
  
  CONCLUSIONS
  This study indicated that 3,4-DAP base pharmacokinetics were non-linear. Although no clinically significant changes in ECG were observed, it is advisable to perform ECG periodically during 3,4-DAP administration in order to monitor cardiac function. Moreover, the development of perioral paresthesia may be dependent on the dose of 3,4-DAP used.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Ishida
authors.forename: Erina
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsushita
authors.forename: Kiyonobu
authors.initials: K
authors.lastname: Komai
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000077770:Amifampridine; D019540:Area Under Curve; D044466:Asian People; D018592:Cross-Over Studies; D004562:Electrocardiography; D005215:Fasting; D006207:Half-Life; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007564:Japan; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009431:Neural Conduction / Q000187:drug effects; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D017711:Nonlinear Dynamics; D019518:Postprandial Period; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009465:Neuromuscular Agents; D015761:4-Aminopyridine; D000077770:Amifampridine