Bioavailability of S(+)‐Ketoprofen After Oral Administration of Different Mixtures of Ketoprofen Enantiomers to Dogs

Abstract

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. [ 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 [ C]-S(+)-ketoprofen was observed on going from treatment E (lowest dose of S-enantiomer) to treatments containing the highest doses of ( C]-S(+)-ketoprofen. When the pharmacokinetic calculations were normalized to the dose of ( C]-S(+)-ketoprofen, we found no statistically significant differences among the normalized AUC and C 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 values among treatments, indicating that the rate of S(+)-ketoprofen absorption was also unaffected by the presence of R(-)-ketoprofen.

Ketoprofen Uygulamasının Süt İneklerindeki Erken Laktasyon Döneminde Lipit Mobilizasyon, Ketogenez ve Metabolik Adaptasyon Üzerine Etkisi

“…As a NSAID, the primary mechanism of action of ketoprofen is a reversible inhibition of the cyclooxygenase enzyme, and a reduced biosynthesis of thromboxane A 2 and prostaglandin from arachidonic acid [19][20][21] . Ketoprofen inhibits both isoforms of the COX enzyme, although it is considered as a COX-1 selective drug [22,23] and it is used extensively in human and veterinary medicine.…”