Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age

Abstract

Following intravenous dose of 6mg/kg racemic ketoprofen, the chiral pharmacokinetics of ketoprofen was investigated in eight piglets aged 6 and 21days 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 3.4h for both age groups, while the elimination half-life of R-ketoprofen was 0.2h for the 6-day-old and 0.4h 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.

PK/PD modeling of flunixin meglumine in a kaolin‐induced inflammation model in piglets

“…The pharmacokinetic parameters of flunixin recorded in the present study were very similar to the results from a recent study performed in mature swine (Pairis‐Garcia et al., ). However, pharmacokinetic parameters have been shown to vary with age (Fosse, Horsberg et al., ), breed (Howard et al., ), and experimental setting. Therefore, comparisons of the pharmacokinetic parameters should be done with caution.…”

“…Recently, the pharmacokinetics of flunixin was described in adult pigs after intravenous, intramuscular, and oral administration (Buur, Baynes, Smith, & Riviere, ; Pairis‐Garcia et al., ). Pharmacokinetic profiles may be influenced by age, and piglets may not require similar dose regimen as adult swine (Fosse, Horsberg et al., ). Despite the fact that flunixin is marketed for pigs and also used clinically in piglets, there is, to our knowledge, only scarce information on dosage and efficacy of this NSAID in piglets.…”

Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

“…The absolute bioavailability of both ketoprofen enantiomers after IM administration is suggested to be almost complete [13,31]. After PO administration the bioavailability is reported to be approximately 85 % for both enantiomers [14].…”

“…The enantioselectivity differences in clearance may be attributable to differences in distribution, chiral inversion, hepatic metabolism, renal excretion, or to a combination of these factors. The volume of distribution is low for ketoprofen in pigs, probably due to high protein binding [13]. The degree of stereo selectivity in binding to plasma or tissue proteins, which is species dependent, may result in a significant effect on the amount of drug in the plasma [36].…”

“…In most species, including horses [12] and pigs [13,14], S-ketoprofen is the predominant enantiomer in the plasma after administration of the racemic drug, whilst R-ketoprofen is predominant in sheep [15]. The plasma concentrations of both enantiomers are similar in goats [16] and calves [17].…”