Human plasma concentrations of R, S, and racemic flurbiprofen given as a toothpaste.
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 (tmax) 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.
Forland
S C
SC
Medical Center, Loma Linda University, California 92354, USA.
Wechter
W J
WJ
Witchwoot
S
S
Clifford
K H
KH
Arnett
R L
RL
Cutler
R E
RE
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005480:Flurbiprofen / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D009055:Mouth / Q000378:metabolism*; D013237:Stereoisomerism; D014100:Toothpastes
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014100:Toothpastes; D005480:Flurbiprofen