title: Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses.
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, t1/2 beta 0.99 +/- 0.14 h, 0.70 +/- 0.13 h; ClB 0.56 +/- 0.09, 0.92 +/- 0.20 L/h/kg; Vd(ss) 0.53 +/- 0.11, 0.61 +/- 0.10 L/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 on the feeding schedule.
authors.affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, Hatfield Herts, United Kingdom.
authors.forename: M F
authors.initials: MF
authors.lastname: Landoni
authors.forename: P
authors.initials: P
authors.lastname: Lees
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D005260:Female; D005508:Food Deprivation; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D007408:Intestinal Absorption / Q000187:drug effects; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D009824:Ointments; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D009824:Ointments; D007660:Ketoprofen