Linked Life Data

7874071

Source:http://linkedlifedata.com/resource/pubmed/id/7874071

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1995-4-5
pubmed:abstractText
To further clarify the pharmacokinetic characteristics of phenytoin (DPH) and its derivatives, DPH-1-methylnicotininate (MNDPH), valeroyl DPH (VADPH) and valproyl DPH (VPDPH), in plasma and brain, we have investigated their physicochemical properties and protein binding characteristics. Additionally, the hydrolytic conversion of these derivatives to DPH was also studied using small intestine, liver and brain tissues, as well as rat plasma. The log partition coefficient (PC) values of all derivatives were much higher than that of DPH. Judging from their pKa values (5.68 and 5.91 for VADPH and VPDPH, respectively) and pH-solubilities, VADPH and VPDPH were acidic compounds, while MNDPH was basic. These data indicated that most fractions of VADPH and VPDPH existed as an ionized form (these fractions existed in an ionized form, 0.98 and 0.97, respectively) at physiological pH, whereas MNDPH existed as a unionized form under the same conditions. Rosenthal or Scatchard plots of the binding data of DPH and its derivatives to both rat plasma protein and bovine serum albumin (BSA) exhibited straight lines over their concentration ranges used, indicating that DPH and its derivatives have a single binding site on the protein. The binding potencies (K or n.Pt value) of the derivatives to both proteins were much greater than that of DPH. No DPH produced from VADPH and VPDPH was found in the biological fluids over a period of 24 h. However, the hydrolysis of MNDPH to DPH was observed in plasma and the tissues used, with the most rapid hydrolysis in the small intestine, and the hydrolysis rate constant in plasma was ca. 20-fold greater than that in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0918-6158
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1425-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Physicochemical and hydrolytic characteristics of phenytoin derivatives.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
pubmed:publicationType
Journal Article, In Vitro