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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1990-2-1
|
| pubmed:abstractText |
The bioavailability and pharmacokinetics of an oral dopamine prodrug, N-(N-acetyl-L-methionyl)O,O-bis(ethoxycarbonyl)dopamine (1), were examined in dogs, and the mechanism of its absorption and bioactivation was discussed. Compound 1 showed a plasma dopamine concentration that was several times higher than that of dopamine (DA) following oral administration to dogs, while the plasma concentrations of dopamine-30-sulfate (DA-SO4) and 3,4-dihydroxyphenylacetic acid (DOPAC) are lower in comparison with that of DA. The conversion of 1 to DA occurred in proportion to the dose administered. Compound 1 also showed a plasma DA concentration that was several times higher than that of other DA prodrugs reported hitherto. In dog plasma, in vitro, 1 was converted to its deethoxycarbonylated form, N-(N-acetyl-L-methionyl)dopamine (2), while other related compounds, N-(L-methionyl)dopamine (3), N-(L-methionyl)O,O-bis(ethoxycarbonyl)-dopamine (4), and O,O-bis(ethoxycarbonyl)dopamine (5), were rapidly converted to DA (however, 2 was stable in plasma). Bioavailability, based on the AUC of DA, 1, 2, and 5 following oral administration to dogs, increased in the following order: 1, 2, 5, and DA. Thus, it was shown that the two protective groups introduced in 1 served to reduce the first-pass metabolism of the DA moiety in the absorption process. It was also confirmed that 1 is converted to 2 or DA in blood, liver, and intestine.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0022-3549
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
78
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
812-4
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:2600785-3,4-Dihydroxyphenylacetic Acid,
pubmed-meshheading:2600785-Administration, Oral,
pubmed-meshheading:2600785-Animals,
pubmed-meshheading:2600785-Biological Availability,
pubmed-meshheading:2600785-Biotransformation,
pubmed-meshheading:2600785-Dogs,
pubmed-meshheading:2600785-Dopamine,
pubmed-meshheading:2600785-Drug Stability,
pubmed-meshheading:2600785-Duodenum,
pubmed-meshheading:2600785-Injections,
pubmed-meshheading:2600785-Intestinal Absorption,
pubmed-meshheading:2600785-Intubation, Gastrointestinal,
pubmed-meshheading:2600785-Mesenteric Veins,
pubmed-meshheading:2600785-Prodrugs
|
| pubmed:year |
1989
|
| pubmed:articleTitle |
Bioavailability and pharmacokinetics of an oral dopamine prodrug in dogs.
|
| pubmed:affiliation |
Products Formulation Research Laboratory, Tanabe Seiyaku Company, Ltd., Osaka, Japan.
|
| pubmed:publicationType |
Journal Article
|