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Human Plasma Concentrations of R, S , and Racemic Flurbiprofen Given as a Toothpaste
Author(s) -
Forland Steven C.,
Wechter William J.,
Witchwoot Sooky,
Clifford Kay H.,
Arnett R. Leslie,
Cutler Ralph E.
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.tb05044.x
Subject(s) - flurbiprofen , chemistry , bioavailability , pharmacokinetics , oral administration , pharmacology , chromatography , medicine
Flurbiprofen, an arylpropionic acid (APA) class nonsteroidal antiinflammatory drug (NSAID), is commercially available only as the racemic mixture, although its pharmacologic effect has been credited primarily to the S isomer. In humans, the bioavailability of racemic flurbiprofen absorbed from the oral cavity has been studied measuring the total concentration of S‐ and R‐ flurbiprofen, and the pharmacokinetics of S‐ and R‐ flurbiprofen have been studied after oral administration of racemic flurbiprofen. In this study, the plasma concentrations of S‐ flurbiprofen and to some extent R‐ flurbiprofen were studied after brushing with a toothpaste containing different mixtures of S‐ and R‐ flurbiprofen. The toothpaste formulations contained 1% racemic (50:50), eutectic (14:86), 1%, 0.5%, and 0.25% (5:95) R‐ to S‐ flurbiprofen. Both S‐ and R‐ flurbiprofen were rapidly absorbed, with a time to reach maximum concentration (t max ) of 1.2 to 1.4 hours. Based on the AUC, the amount of S‐ flurbiprofen absorbed increased proportionally when given as the 0.25% (5:95) preparation to the 0.5% (5:95) mixture but did not increase significantly above the 0.5% (5:95) mixture when given as 1% (5:95) R‐ to S‐ flurbiprofen. This suggests that dose‐proportional absorption of S‐ flurbiprofen is not maintained at higher concentrations. The elimination of S‐ flurbiprofen appears to be variable and prolonged after this mode of administration, as observed from plasma concentrations. Further controlled and more prolonged studies of S‐ and R‐ flurbiprofen are needed to confirm these observations .