Bioavailability of S(+)-ketoprofen after oral administration of different mixtures of ketoprofen enantiomers to dogs

Recent reports have disagreed on whether the bioavailability of S(+)-ketopr ofen is affected by the presence of R(-)-ketoprofen. To examine this direct ly, we designed a randomized crossover study in beagle dogs. [C-14] S(+)-ke toprofen trometamol and R(-)-ketoprofen trometamol were administered in the following percentage ratios: A, 99:1; B, 95:5; C, 90:10; D, 70:30; E, 50:5 0. Treatments were administered as a single oral dose of I mg/kg trometamol salt. Each of eight dogs received all five combinations in random order wi th a 1-week washout period between doses. Blood samples were taken before d rug administration and at regular intervals for 240 min after dosing. A pro gressive increase in the plasma concentration of [C-14]-S(+)-ketoprofen was observed on going from treatment E (lowest dose of S-enantiomer) to treatm ents containing the highest doses of [C-14]-S(+)-ketoprofen, When the pharm acokinetic calculations were normalized to the dose of [C-14]-S(+)ketoprofe n, we found no statistically significant differences among the normalized A UC and C-max values of the Jive treatments. Therefore, S(+)-ketoprofen abso rption was linear and rt as not influenced by the presence of R(-)-ketoprof en. Furthermore, there were no significant differences in t(max) values amo ng treatments, indicating that the rate of S(+)-ketoprofen absorption was a lso unaffected by the presence of R(-)-ketoprofen. Journal of Clinical Phar macology, 1998;38:228-26S (C) 1998 The American College of Clinical Pharmac ology.