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In vitro Enantioselective Glucuronidation of Fenoprofen
- Source :
- Pharmacology. 43:53-60
- Publication Year :
- 1991
- Publisher :
- S. Karger AG, 1991.
-
Abstract
- The diastereomeric glucuronic acid conjugates are major metabolites of the nonsteroidal anti-inflammatory drug fenoprofen (FEN). Glucuronidation of FEN enantiomers was investigated with liver microsomal preparations from different species (sheep, rabbit, rat and human). The formed R- and S-FEN conjugates can be separated and quantitated directly on a C18 reversed-phase HPLC column using a mixture of acetonitrile and tetrabutylammonium sulfate buffer, pH 2.5, as mobile phase. Applying this analytical procedure, it is possible to characterize enantioselective glucuronidation of FEN. For in vitro procedures, rates of glucuronide formation are substrate (FEN) and cosubstrate (UDP glucuronic acid, UDPGA) dependent with initial rates of glucuronide formation being higher for R- than for S-FEN. The R/S ratio of the formed products was independent of UDPGA (2.5-15 mmol/l) and substrate concentrations greater than or equal to 0.4 mmol/l. Enantioselective cleavage of the formed FEN conjugates by alkaline hydrolysis and hydrolytic enzymes (R greater than S-glucuronide) can be controlled during in vitro studies by pH adjustment and the addition of enzyme inhibitors.
- Subjects :
- Stereochemistry
Glucuronidation
Glucuronates
Alkaline hydrolysis (body disposal)
Hydrolysis
chemistry.chemical_compound
Fenoprofen
medicine
Animals
Humans
Chromatography, High Pressure Liquid
Pharmacology
Sheep
Chromatography
Chemistry
Substrate (chemistry)
Stereoisomerism
General Medicine
Hydrogen-Ion Concentration
Glucuronic acid
Rats
Microsomes, Liver
Uridine Diphosphate Glucuronic Acid
Rabbits
Enantiomer
Glucuronide
medicine.drug
Subjects
Details
- ISSN :
- 14230313 and 00317012
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Pharmacology
- Accession number :
- edsair.doi.dedup.....3437a0e719f7897daba7ef09a945e135