Effect of dimethicone (polysilane gel) on the stereoselective pharmacokinetics of ketoprofen.
OBJECTIVE
Since dimethicone may be employed to improve gastrointestinal tolerability of non steroidal anti-inflammatory drugs (NSAIDs), we studied its influence on the pharmacokinetics of ketoprofen in subjects receiving a single oral dose of racemic ketoprofen.


METHODS
In a cross-over experimental design, 12 healthy fasting volunteers were given a single oral dose (100 mg) of racemic ketoprofen, administered with or without dimethicone. The kinetic parameters measured were area under the concentration (AUC), maximum peak plasma concentration (Cmax), time to reach peak concentration (tmax), elimination half-life (t1/2), mean residence time (MRT) and urinary excretion for R and S enantiomers.


RESULTS
Dimethicone reduced the peak concentration of both R and S ketoprofen by about 10% (P<0.05) and also induced a slight but non-significant increase in the mean time to achieve peak concentration. However, this treatment had no significant effect on the bioavailability and the elimination of R and S enantiomers, as shown by AUC, t1/2 and MRT values. The absorption patterns were equivalent for both ketoprofen isomers, since plasma pharmacokinetic parameters were similar. Nevertheless, the urinary recovery was significantly lower for R ketoprofen than for its antipode. The administration of dimethicone did not alter this stereoselectivity.


CONCLUSIONS
The administration of dimethicone to alleviate the epigastralgic effects related to NSAIDs does not affect the efficacy of the treatment. Dimethicone did not significantly alter the bioavailability of ketoprofen, chosen as an example of an NSAID, especially that of the pharmacologically active S enantiomer.
Laboratoire de Pharmacologie UMR 7561 CNRS-UHP Nancy 1, Faculté de Médecine, Vandoeuvre les Nancy, France. netter@pharmaco-med.u-nancy.fr
N
N
Presle
F
F
Lapicque
P
P
Gillet
M A
MA
Herrmann
B
B
Bannwarth
P
P
Netter
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D007660:Ketoprofen / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D012841:Simethicone / Q000494:pharmacology*; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D012841:Simethicone; D007660:Ketoprofen