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. [14C]-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 tromnetamol salt. Each of eight dogs received all five combinations in random order with a 1-week wash-out 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 [14C]-S(+)-ketoprofen was observed on going from treatment E (lowest dose of Senantiomer) to treatments containing the highest doses of [14C]-S(+)-ketoprofen. When the pharmacokinetic calculations were normalized to the dose of [14C]-S(+)-ketoprofen, we found no statistically significant differences among the normalized AUC and Cmax 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 tmax values among treatments, indicating that the rate of S(+)-ketoprofen absorption was also unaffected by the presence of R(-)-ketoprofen.
García
M L
ML
R&D Department, Laboratorios Menarini S.A., Badalona, Spain. lgarcia@menarini.es
Tost
D
D
Vilageliu
J
J
López
S
S
Carganico
G
G
Mauleón
D
D
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004285:Dogs; D007660:Ketoprofen / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D011897:Random Allocation; D013237:Stereoisomerism; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014325:Tromethamine; D007660:Ketoprofen; C118296:dexketoprofen trometamol