Human plasma concentrations of R, S, and racemic flurbiprofen given as a toothpaste

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Medicinal Chemistry

Background:

• Flurbiprofen, an arylpropionic acid (APA) nonsteroidal antiinflammatory drug (NSAID), is typically sold as a racemic mixture.
• The therapeutic effects of flurbiprofen are primarily attributed to its S-isomer.
• Previous studies have examined flurbiprofen bioavailability and pharmacokinetics following oral administration.

Purpose of the Study:

• To investigate the plasma concentrations of S- and R-flurbiprofen after administration via a novel toothpaste formulation.
• To evaluate the dose-proportionality and absorption characteristics of flurbiprofen isomers delivered through oral brushing.

Main Methods:

• Toothpaste formulations containing varying ratios of R- to S-flurbiprofen (racemic 50:50, eutectic 14:86, and 5:95 at 1%, 0.5%, and 0.25%) were prepared.
• Plasma concentrations of S- and R-flurbiprofen were measured after participants brushed their teeth with the formulations.
• Key pharmacokinetic parameters, including time to maximum concentration (tmax) and area under the curve (AUC), were analyzed.

Main Results:

• Both S- and R-flurbiprofen were rapidly absorbed, with a tmax of 1.2 to 1.4 hours.
• The absorption of S-flurbiprofen increased proportionally with doses from 0.25% to 0.5% (5:95 R:S ratio).
• Dose-proportional absorption of S-flurbiprofen was not observed at higher concentrations (1% of 5:95 R:S ratio), and elimination appeared variable and prolonged.

Conclusions:

• Flurbiprofen delivered via toothpaste shows rapid absorption, but dose-proportionality may be limited at higher concentrations.
• The elimination of S-flurbiprofen following this administration route may be variable.
• Further research is warranted to confirm these findings with controlled, extended studies.