Document Detail


In vivo microdialysis to determine the relative pharmacokinetics of drugs.
MedLine Citation:
PMID:  8839975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to evaluate a simultaneous microdialysis method in blood and brain striatum to determine the relative pharmacokinetics and metabolism of L-3,4-dihydroxypenylalanine (L-dopa). L-Dopa (250 mumol/kg) was administered to rats with or without the aromatic amino acid decarboxylase (AADC) inhibitor carbidopa (25 mumol/kg) or benserazide (25 or 62.5 mumol/kg). L-Dopa, its metabolites, and AADC inhibitors in dialysates were analyzed by high performance liquid chromatography with an electrochemical detector. A moment analysis was also made to obtain pharmacokinetic parameters. After administration of L-dopa alone, it and its related metabolites were detected in both dialysates of blood and brain striatum. Coadministration of carbidopa (25 mumol/kg) or benserazide (62.5 mumol/kg) significantly enhanced the striatal amount of L-dopa by 8.0 and 6.1 times, respectively. Carbidopa and benserazide also increased striatal amounts of L-dopa metabolites, such as 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol. Inhibition effect of benserazide on an extracerebral decarboxylation of L-dopa to dopamine (DA) was stronger than that of carbidopa. Carbidopa showed a higher striatal level of DA than benserazide. These results suggest a different effect of the two inhibitors on the DA formations in blood and brain striatum, and on the L-dopa transport through the blood-brain barrier (BBB). Thus, microdialysis is an easy and available method for simultaneously assessing the in vivo relative pharmacokinetics and metabolism of drugs in systemic circulation and a target organ.
Authors:
M Nakashima; M F Zhao; M N Nakashima; M Sakurai; H Sasaki; K Matsuyama; M Ichikawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  19     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1997-01-30     Completed Date:  1997-01-30     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  988-94     Citation Subset:  IM    
Affiliation:
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
Animals
Antiparkinson Agents / pharmacokinetics*
Benserazide / pharmacokinetics
Brain Chemistry / drug effects
Carbidopa / pharmacokinetics
Chromatography, High Pressure Liquid
Dopamine / metabolism
Drug Interactions
Electrochemistry
Homovanillic Acid / metabolism
Levodopa / pharmacokinetics*
Male
Methoxyhydroxyphenylglycol / metabolism
Microdialysis / methods*
Neostriatum / chemistry,  metabolism
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Levodopa; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 306-08-1/Homovanillic Acid; 322-35-0/Benserazide; 38821-49-7/Carbidopa; 534-82-7/Methoxyhydroxyphenylglycol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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