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(+)‐ketoprofen is affected by the presence of R(−)‐ketoprofen. To examine this directly, we designed a randomized crossover study in beagle dogs. [ 14 C]‐ S(+)‐ketoprofen 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, 50:50. Treatments were administered as a single oral dose of 1 mg/kg trometamol salt. Each of eight dogs received all five combinations in random order with a 1‐week washout period between doses. Blood samples were taken before drug administration and at regular intervals for 240 min after dosing. A progressive increase in the plasma concentration of [ 14 C]‐S(+)‐ketoprofen was observed on going from treatment E (lowest dose of S‐enantiomer) to treatments containing the highest doses of ( 14 C]‐S(+)‐ketoprofen. When the pharmacokinetic calculations were normalized to the dose of ( 14 C]‐S(+)‐ketoprofen, we found no statistically significant differences among the normalized AUC and C max values of the five treatments. Therefore, S(+)‐ketoprofen absorption was linear and was not influenced by the presence of R(−)‐ketoprofen. Furthermore, there were no significant differences in t max values among treatments, indicating that the rate of S(+)‐ketoprofen absorption was also unaffected by the presence of R(−)‐ketoprofen.