title: Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic, potentially highly disabling neurological disorder. No disease-modifying treatments are approved in the progressive and not active forms of the disease.
  
  
  METHODS
  High doses of biotin were tested in an open-label pilot study involving 23 patients with progressive MS and reported positive results. A randomized, double-blind, placebo-controlled trial in 154 progressive MS patients confirmed the beneficial effect of MD1003 (high-dose biotin) on reversing or stabilizing disability progression, with a good safety profile. It is proposed that MD1003 in progressive MS 1) increases energy production in demyelinated axons and/or 2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid. The major route of elimination is urinary excretion.
  
  
  CONCLUSIONS
  A high oral dose of biotin seems generally well tolerated but a few important safety concerns were identified: 1) teratogenicity in one species and 2) interference with some biotin-based laboratory immunoassays. The animal toxicity data are limited at such high doses. Further preclinical studies would be useful to address the mechanism of action of MD1003. Assessment of clinical benefit duration in responders will be also very important to set. Results of randomized, placebo-controlled trial are reassuring and provide hope for the treatment of progressive MS.
authors.affiliation: a Clinical Research , Centre Hospitalier Universitaire de Caen , Caen , France.
authors.forename: Laure
authors.initials: L
authors.lastname: Peyro Saint Paul
authors.affiliation: b Pharmacology , Centre Hospitalier Universitaire de Caen , Caen , France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Debruyne
authors.affiliation: c MedDay Pharmaceuticals , ICM-Brain and Spine Institute-IPEPs, Groupe Hospitalier Pitié Salpêtrière , Paris , France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bernard
authors.affiliation: d Department of Biochemistry & Molecular Biology and Pediatrics , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Mock
authors.affiliation: e Neurology , Centre Hospitalier Universitaire de Caen , Caen , France.|f INSERM U 919 , GIP Cyceron , Caen , France.
authors.forename: Gilles L
authors.initials: GL
authors.lastname: Defer
mesh_terms: D000818:Animals; D001682:Biological Availability; D001710:Biotin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D014803:Vitamin B Complex; D001710:Biotin
keywords: Biotin; energy metabolism; pharmacodynamics; pharmacokinetics; progressive multiple sclerosis; remyelination