| Bioavailability improvement of mycophenolic acid through amino ester derivatization. | |
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MedLine Citation:
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PMID: 2308896 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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W A Lee; L Gu; A R Miksztal; N Chu; K Leung; P H Nelson |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Pharmaceutical research Volume: 7 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1990 Feb |
Date Detail:
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Created Date: 1990-04-02 Completed Date: 1990-04-02 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 161-6 Citation Subset: IM |
Affiliation:
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Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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24280-93-1/Mycophenolic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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