Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man.
AIMS: 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.