Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man

Abstract

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 (C max ) 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, C max /AUC was increased by buffering. Time to C max (t max ) 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.

Pharmacodynamics, chiral pharmacokinetics and PK–PD modelling of ketoprofen in the goat

“…Enantioselective pharmacokinetics of KTP has not only been demonstrated in several species, including human, rat, rabbit, dog, cat, cow, sheep and horse, but also found to differ quantitatively between species (Abas & Meffin, 1987; Caldwell et al , 1988; Foster & Jamali, 1988; Delatour et al ., 1993, 1994; Jaussaud et al ., 1993; Mauleon et al ., 1994; Landoni & Lees, 1995a,b, 1996b; Landoni et al ., 1995, 1999; Skeith et al ., 1996, Arifah et al ., 2001). There is overall predominance (measured as plasma concentration) after rac‐KTP administration of S (+) KTP in the rat, rabbit, dog, cat, monkey and horse (Abas & Meffin, 1987; Foster & Jamali, 1988; Delatour et al ., 1993, 1994; Jaussaud et al ., 1993; Mauleon et al ., 1994; Landoni & Lees, 1995a,b; Brink et al ., 1998) and of R (−) KTP in sheep (Delatour et al ., 1994; Landoni et al ., 1999; Arifah et al ., 2001), whilst plasma concentrations of the two enantiomers are similar in humans and cattle (Sallustio et al ., 1988; Delatour et al ., 1994; Geisslinger et al ., 1995; Landoni et al ., 1995; Fuder et al ., 1997). This is in spite of the fact that chiral inversion of R (−) to S (+) KTP occurs in humans and cattle.…”

Pharmacokinetics of Dexketoprofen Trometamol in Healthy Volunteers After Single and Repeated Oral Doses

“…26 Moreover, the possibility that maximal plasma concentrations can be increased by increasing the rate of absorption while leaving AUC unaffected has also been recently observed in a study in which ketoprofen was buffered with magnesium hydroxide/ citrate. 27 In the first 12 h after all treatments, 73.3-81.9% of the administered dose was recovered in the urine, suggesting that the excretion of both S( + )-ketoprofen and racemic ketoprofen is mainly renal. It was excreted principally as the acyl-glucuronoconjugate, in good agreement with the results previously described by Foster et al 28 The recovery of racemic ketoprofen in urine was measured as a mixture of Rand S-enantiomers because bioinversion changes the R:S ratio.…”

Application of FTIR Spectroscopic Imaging to Study the Effects of Modifying the pH Microenvironment on the Dissolution of Ibuprofen from HPMC Matrices

“…[7][8][9] Less work exists on the use of pH modifiers for modifying the release of weakly acidic drugs. [10][11][12][13] Upon addition of ionic species to the matrix, salts may be formed with oppositely charged drugs of both low solubility 14 and high solubility. While using pHmodified formulations, the pH is adjusted within the tablet matrix; therefore, it is important to understand the behavior of the drug within the matrix.…”