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Safety, Tolerability, and Cerebrospinal Fluid Penetration of Ursodeoxycholic Acid in Patients With Amyotrophic Lateral Sclerosis
- Source :
- Clinical Neuropharmacology. 33:17-21
- Publication Year :
- 2010
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2010.
-
Abstract
- Objective Amyotrophic lateral sclerosis is a progressive degenerative disease, which typically leads to death in 3 to 5 years. Neuronal cell death offers a potential target for therapeutic intervention. Ursodeoxycholic acid is a cytoprotective, endogenous bile acid that has been shown to be neuroprotective in experimental Huntington and Alzheimer diseases, retinal degeneration, and ischemic and hemorrhagic stroke. The objective of this research was to study the safety and the tolerability of ursodeoxycholic acid in amyotrophic lateral sclerosis and document effective and dose-dependent cerebrospinal fluid penetration. Methods Eighteen patients were randomly assigned to receive ursodeoxycholic acid at doses of 15, 30, and 50 mg/kg of body weight per day. Serum and cerebrospinal fluid were obtained for analysis after 4 weeks of treatment. Treatment-emergent clinical and laboratory events were monitored weekly. Results Our data indicated that ursodeoxycholic acid is well tolerated by all subjects at all doses. We also showed that ursodeoxycholic acid is well absorbed after oral administration and crosses the blood-brain barrier in a dose-dependent manner. Conclusions These results show excellent safety and tolerability of ursodeoxycholic acid. The drug penetrates the cerebrospinal fluid in a dose-dependent manner. A large, placebo-controlled clinical trial is needed to assess the efficacy of ursodeoxycholic acid in treating amyotrophic lateral sclerosis.
- Subjects :
- Adult
Male
Cholagogues and Choleretics
medicine.medical_specialty
Pathology
Time Factors
medicine.drug_class
Gastroenterology
Bile Acids and Salts
Cerebrospinal fluid
Double-Blind Method
Oral administration
Internal medicine
medicine
Humans
Pharmacology (medical)
Amyotrophic lateral sclerosis
Stroke
Aged
Pharmacology
Analysis of Variance
Dose-Response Relationship, Drug
Bile acid
business.industry
Amyotrophic Lateral Sclerosis
Ursodeoxycholic Acid
Drug Tolerance
Middle Aged
medicine.disease
Ursodeoxycholic acid
Treatment Outcome
Tolerability
Blood-Brain Barrier
Cerebrospinal fluid penetration
Female
Neurology (clinical)
business
medicine.drug
Subjects
Details
- ISSN :
- 03625664
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Clinical Neuropharmacology
- Accession number :
- edsair.doi.dedup.....d8dfdd99ae72736a86747ddb7c9b1a9d