Document Detail


Bioavailability improvement of mycophenolic acid through amino ester derivatization.
MedLine Citation:
PMID:  2308896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The potential bioavailability improvement of mycophenolic acid (MPA), 1, through ester derivatization was evaluated in monkeys at a dose of 20 mg/kg in this study. The acetyl solketal ester 3 was found to have excellent partition properties but poor aqueous solubility. Thus, even though it can be converted rapidly to MPA by plasma and liver enzymes, it showed poor oral bioavailability (56% of MPA) in monkeys. The bioavailability of the morpholinoethyl ester 4 and the acetyl morpholinoethyl ester 5, on the other hand, was found to be 236 and 150% that of MPA, respectively. Since ester 5 has greater aqueous solubility, but similar chemical stability and enzymatic hydrolysis rates compared to ester 4, the better bioavailability of ester 4 may result from its greater partitioning into the gastrointestinal membranes.
Authors:
W A Lee; L Gu; A R Miksztal; N Chu; K Leung; P H Nelson
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Pharmaceutical research     Volume:  7     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  1990 Feb 
Date Detail:
Created Date:  1990-04-02     Completed Date:  1990-04-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  161-6     Citation Subset:  IM    
Affiliation:
Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Biological Availability
Chemistry, Physical
Chromatography, High Pressure Liquid
Humans
Liver / metabolism
Macaca fascicularis
Mice
Mycophenolic Acid / administration & dosage,  analogs & derivatives,  pharmacokinetics*
Physicochemical Phenomena
Solubility
Species Specificity
Chemical
Reg. No./Substance:
24280-93-1/Mycophenolic Acid

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


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