Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age T. K. FOSSE* T. E. HORSBERG* H. A. HAGA   V. HORMAZABAL* & B. RANHEIM* *Department of Food Safety and Infection Biology, The Norwegian School of Veterinary Science, Oslo, Norway;  Department of Companion Animal Clinical Sciences, The Norwegian School of Veterinary Science, Oslo, Norway Fosse, T. K., Horsberg, T. E., Haga, H. A., Hormazabal, V., Ranheim, B. Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age. J. vet. Pharmacol. Therap. 34, 153–159. Following intravenous dose of 6 mg ⁄ kg racemic ketoprofen, the chiral pharmacokinetics of ketoprofen was investigated in eight piglets aged 6 and 21 days old. S-ketoprofen predominated over R-ketoprofen in plasma of the piglets in both age groups. The volumes of distribution of S-ketoprofen for the 6- and 21-day-old piglets were 241.7 (211.3–276.5) mL ⁄ kg and 155.0 (138.7–173.1) mL ⁄ kg, respectively, while the corresponding parameters for R-ketoprofen were 289.2 (250.3–334.2) mL ⁄ kg and 193.0 (168.7–220.8) mL ⁄ kg. The clearances of R-ketoprofen [948.4 (768.0–1171.2) mL ⁄ h ⁄ kg and 425 (319.1–566.0) mL ⁄ h ⁄ kg for the 6- and 21-day-old piglets, respectively] were significantly higher compared to the clearances of S-ketoprofen [57.3 (46.6–70.4) mL ⁄ h ⁄ kg and 33.8 (27.0–42.2) mL ⁄ h ⁄ kg for 6- and 21-day-old piglets, respectively]. The elimination half-life of S-ketoprofen was 3.4 h for both age groups, while the elimination half-life of R-ketoprofen was 0.2 h for the 6-day-old and 0.4 h for the 21-day-old piglets. The clearances of both R- and S-ketoprofen were significantly higher in the 6-day-old piglets compared to when they were 21 days old. Furthermore, the volumes of distribution were larger in the youngest age group. (Paper received 8 January 2010; accepted for publication 28 March 2010) Torunn Krangnes Fosse, Department of Food Safety and Infection Biology, The Norwegian School of Veterinary Science, PO Box 8146 Dep., N-0033 Oslo, Norway. E-mail: torunn.fosse@nvh.no INTRODUCTION Ketoprofen (2-(phenyl 3-benzoyl) propionic acid) is a nonsteroi- dal anti-inflammatory drug (NSAID) of the 2-arylpropionic acid group (generically known as profens) that has analgesic, anti- inflammatory and antipyretic properties. In pigs, it is marketed as an anti-inflammatory and analgesic support treatment for respiratory diseases and for mastitis-metritis-agalactia syndrome in sows. Ketoprofen may also be used as an analgesic and anti- inflammatory agent in piglets following painful procedures such as castration and tail-docking and after traumatic injuries and inflammatory joint diseases. Whereas routine surgical proce- dures are usually performed during the first week of life (Fredriksen et al., 2009), inflammatory conditions such as arthritis can occur throughout the entire suckling period (Zoric et al., 2003). Ketoprofen is a chiral compound that contains one asymmetric carbon atom and thus exists in two enantiomeric forms. It is licensed for use in animals as the racemic (50:50) mixture of the two enantiomers, R- and S-ketoprofen. Apart from their ability to rotate plane-polarized light, enantiomers have identical chemical and physical properties. However, given that the body is a highly chiral environment, the pharmacokinetic and pharmacodynamic properties of the two enantiomers may differ profoundly. In general, the S-enantiomer of ketoprofen is regarded as a several times more potent inhibitor of cyclo- oxygenases than the R-enantiomer (Suesa et al., 1993). How- ever, potency differences between the two enantiomers are likely to exist between species. Enantioselective pharmacokinetics of racemic ketoprofen has been demonstrated in several species (Delatour et al., 1993). To our knowledge, there is only one publication describing the pharmacokinetics of ketoprofen in pigs (Raekallio et al., 2008) but in this study, only ‘‘total drug’’ concentrations and not the individual enantiomers were reported. The presence of physio- logical differences between neonatal and adult animals can affect the pharmacokinetics of drugs. Characteristic features of the pharmacokinetics of NSAIDs in neonatal animals include a larger volume of distribution, lower clearance and longer elimination half-life compared to adults (Lees et al., 2004). Igarza et al. (2004) showed that newborn calves had lower clearance and longer elimination half-life of ketoprofen com- pared to adult cows. Knowledge of the pharmacokinetics of ketoprofen in piglets during the first month of life is necessary for effective and safe use of the drug in this age group. J. vet. Pharmacol. Therap. 34, 153–159. doi: 10.1111/j.1365-2885.2010.01205.x. Ó 2010 Blackwell Publishing Ltd 153