Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man.
OBJECTIVE
Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.


METHODS
Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p. l.c. up to 24 h post-dose.


RESULTS
Maximum plasma concentrations (Cmax) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50-80%. The area under concentration-time data (AUC) was unaffected, and, hence, Cmax/AUC was increased by buffering. Time to Cmax (tmax) and mean residence time (MRT) tended to be or was shortened by buffering.


CONCLUSIONS
It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.
Fuder
H
H
Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Grünstadt, Germany.
Stiegler
S
S
Wetzelsberger
N
N
Wieckhorst
G
G
Lange
R
R
Lücker
P W
PW
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D002951:Citrates / Q000494:pharmacology; D018592:Cross-Over Studies; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D007660:Ketoprofen / Q000737:chemistry / Q000493:pharmacokinetics*; D008276:Magnesium Hydroxide / Q000494:pharmacology; D008297:Male; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002021:Buffers; D002951:Citrates; D005765:Gastrointestinal Agents; D007660:Ketoprofen; D008276:Magnesium Hydroxide