Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses

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Abstract
The bioavailability of S(+) and R(‐) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil‐based paste containing micronised rac‐KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil‐based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intravenous administration of rac‐KTP, S(+) enantiomer concentrations exceeded those of the R(‐) enantiomer. For S(+) and R(‐)KTP. respectively, pharmacokinetic parameters were, t1/2β 0.99 ± 0.14 h, 0.70 ±0.13 h;C/B 0.56±0.09,0.92±0.20 L/h/kg; Vd(ss), 0.53 ±0.11.0, 61±0.10L/kg. Following oral administration of rac‐KTP as the oil‐based paste to horses with free access to food, there were no detectable concentrations in plasma in three animals at any sampling time, while a fourth animal showed very low concentrations at two sampling times only. In the two remaining horses very low but detectable concentrations were present for 5 h. In the horses with restricted access to food, rac‐KTP paste administration produced higher concentrations in plasma. However, bioavailability was very low, 2.67 ± 0.43 and 5.75 ± 1.48% for R(‐) and S(+)KTP, respectively. When administered as pure drug substance in hard gelatin capsules, absorption of KTP was fairly rapid, but incomplete. Bioavailability was 50.55 ± 10.95 and 54.17 ±9.9% for R(‐) and S(+)KTP, respectively. This study demonstrates that rac‐KTP had a modest bioavailability when administered as a micronised powder in hard gelatin capsules to horses with restricted access to food. When powder from the same source was administered as an oil‐based paste, it was for practical purposes not bioavailable, regardless of the feeding schedule.