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Calculation of Inversion Half‐Lives of Aryl Propionic Acid Class Nonsteroidal Antiinflammatory Drugs
Author(s) -
Kantoci Darko,
Wechter William J.
Publication year - 1996
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1996.tb05039.x
Subject(s) - ketoprofen , enantiomer , prodrug , nonsteroidal , pharmacology , chemistry , inversion (geology) , pharmacokinetics , ibuprofen , aryl , stereochemistry , medicine , organic chemistry , biology , paleontology , alkyl , structural basin
Although inversion of the R‐ enantiomers of the aryl propionic acid (APA) class of nonsteroidal antiinflammatory drugs (NSAIDs) in humans and other mammals has been known for more than 20 years, no satisfactory method has been developed for evaluating the half‐life of the inversion process. This parameter is useful in assessing the pharmacodynamic contribution of the R‐ prodrug to the cyclooxygenase‐inhihiting S‐ enantiomers. Further, it provides a similar means of evaluating the analgesic contribution of R‐ enantiomers to racemic mixtures. Using human and animal data, we have mathematically determined the inversion half‐life (t 1/2i ) for ibuprofen, ketoprofen, and fenoprofen. The relation of the sensitivity of this value to the terminal half‐life (t 1/2 ) of the R‐ enantiomers of APA class drugs also is discussed .