Document Detail


Effects of slowed gastrointestinal motility on levodopa pharmacokinetics.
MedLine Citation:
PMID:  20434962     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Autonomic disorders are often seen in Parkinson's disease, with disturbances of the gastrointestinal tract occurring most frequently. These disorders, mainly a delay in gastric emptying and slowed gastrointestinal motility, can modify the pharmacokinetics and effectiveness of drugs used to treat Parkinson's disease and administered orally. In this study, we evaluated in a rabbit model the pharmacokinetics of levodopa (administered with carbidopa) in the context of gastrointestinal motility slowed by the administration of an anticholinergic drug. Levodopa+carbidopa (20:5mg/kg) and the anticholinergic biperiden (100 microg/kg) were orally administered to rabbits over one of two time periods (7 or 14 days) to verify the stabilization of levodopa concentrations. The values of the area under the curve (AUC) and C(max) were higher on the final day of treatment with an increase in AUC of 25% on day 7 and 33.4% on day 14; for C(max), the increase was 15% on day 7 and 12.8% on day 14. The values of AUC and C(max) were lower than those obtained when levodopa was administered to rabbits with normal gastrointestinal motility. The values obtained for C(min) (baseline sample obtained before administration) also increased with treatment duration (24% and 47.4% on days 7 and 14, respectively). These values were higher than those obtained in the absence of anticholinergic administration. We conclude that, under our experimental conditions of slowed gastrointestinal motility, levodopa absorption diminishes, and final concentrations and C(min) are higher than under conditions of normal motility.
Authors:
Nélida Fernández; Juan J García; M José Diez; Ana M Sahagún; Aranzazu González; Raquel Díez; Matilde Sierra
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Autonomic neuroscience : basic & clinical     Volume:  156     ISSN:  1872-7484     ISO Abbreviation:  Auton Neurosci     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100909359     Medline TA:  Auton Neurosci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  67-72     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Area de Farmacologia, Instituto de Biomedicina, Universidad de Leon, 24071, Leon, Spain. nelida.fernandez@unileon.es
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