Pharmacodynamics and pharmacokinetics of ketoprofen enantiomers in sheep

Arifah, A. K.; Landoni, M. F.; Frean, Stephen P.; Lees, P.

doi:10.2460/ajvr.2001.62.77

Cited by 25 publications

(26 citation statements)

References 30 publications

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“…The elimination half-life of ketoprofen in plasma was higher after the overdose of ketoprofen in the sheep of the present study than in sheep in other studies 25,26 after administration of a frequently used dose of racemic ketoprofen (3 mg/kg) or its enantiomers. Approximately 2 hours after administration of ketoprofen at a dose of 30 mg/kg, the plasma concentration of ketoprofen in our study was at the same value as the maximum concentration reported in sheep after administration at the frequently used dose of 3 mg/kg.…”

Section: Discussioncontrasting

confidence: 48%

“…Approximately 2 hours after administration of ketoprofen at a dose of 30 mg/kg, the plasma concentration of ketoprofen in our study was at the same value as the maximum concentration reported in sheep after administration at the frequently used dose of 3 mg/kg. 25,26 Thus, exposure to the toxic plasma concentration of ketoprofen was probably relatively short, and most of the injuries in the tubular cells can be expected to have taken place during the early phase of our follow-up period.…”

Section: Discussionmentioning

confidence: 99%

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Early detection of ketoprofen-induced acute kidney injury in sheep as determined by evaluation of urinary enzyme activities

Raekallio

Saario-Paunio

Rajamäki³

et al. 2010

ajvr

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Objective-To evaluate early indicators of renal tissue destruction and changes in urinary enzyme activities in sheep during the first hours after acute kidney injury induced by administration of an overdose of an NSAID. Animals-12 adult female sheep. Procedures-Acute kidney injury was induced in 6 sheep by administration of ketoprofen (30 mg/kg, IV) and detected by evaluation of urinary protein concentration, iohexol clearance, and results of histologic examination. Six sheep served as control animals. Blood and urine samples were collected for up to 24 hours after administration of ketoprofen. Plasma concentrations of urea, creatinine, albumin, and total protein; plasma activities of alkaline phosphatase, acid phosphatase, γ-glutamyl transpeptidase (GGT), matrix metalloproteinase (MMP)-2, and MMP-9; and urinary creatinine and protein concentrations, specific gravity, and activities of alkaline phosphatase, acid phosphatase, GGT, lactate dehydrogenase, N-acetyl-β-D-glucosaminidase (NAG), MMP-2, and MMP-9 were measured. Urinary protein concentration and enzyme activities were normalized on the basis of urinary creatinine concentrations and reported as ratios. Results-Many urinary enzyme-to-creatinine ratios increased before the plasma creatinine concentration exceeded the reference value. Urine NAG, lactate dehydrogenase, and acid phosphatase activities were increased beginning at 2 hours after ketoprofen administration, and alkaline phosphatase, GGT, and MMP-2 activities were increased beginning at 4 hours after ketoprofen administration. Most peak urinary enzyme-to-creatinine ratios were detected earlier than were the highest plasma creatinine and urea concentrations. Conclusions and Clinical Relevance-Urinary enzyme activities were sensitive early indicators of acute kidney injury induced by an overdose of an NSAID in sheep. (Am J Vet

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Early detection of ketoprofen-induced acute kidney injury in sheep as determined by evaluation of urinary enzyme activities

Raekallio

Saario-Paunio

Rajamäki³

et al. 2010

ajvr

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“…The authors hypothesized that the former was caused by R-ketoprofen and the later by S-ketoprofen. Ketoprofen concentrations persist for longer in inflammatory exudates than in plasma [15,17,28,45,46], and the clinical effect may therefore last longer than estimated from concentrations in plasma.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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BackgroundKetoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs.MethodsEleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (Frel) was determined for S and R –ketoprofen.ResultsS-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively.ConclusionsAlthough some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs.

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“…Another possible explanation for the more rapid plasma clearance of S-ketoprofen observed in elephants is chiral inversion, in which S-ketoprofen is converted to the R-enantiomer. 30 Selective metabolism of S-ketoprofen to either the hydroxy ketoprofen metabolite or the glycine conjugate reported here would also result in increased Cl p for S-ketoprofen. 19 In the same study, conversion of R-ketoprofen to S-ketoprofen was also reported in mice, gerbils, guinea pigs, rabbits, and cynomolgus monkeys, but this conversion was < 50% of the total ketoprofen dose.…”

Section: Discussionmentioning

confidence: 74%

“…24 Statistical analyses-Pharmacokinetic values obtained for R-ketoprofen and S-ketoprofen following administration by either route were compared by use of Wilcoxon matchedpairs signed-rank tests. [27][28][29][30][31][32][33][34][35] A test for normality was not performed, as it is inappropriate to assume that data obtained from 5 animals are normally distributed. Values are reported as mean, median, and range.…”

Section: Oral Bioavailability and Pharmacokinetic Characteristics Of mentioning

confidence: 99%

Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus)

Hunter¹,

Isaza²,

Koch³

2003

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Pharmacodynamics and pharmacokinetics of ketoprofen enantiomers in sheep

Abstract: Inhibition of serum TXB2 concentration and exudate PGE2 synthesis for similar time courses after S(+) KTP administration indicates that it is a nonselective inhibitor of COX in sheep.

Cited by 25 publications

References 30 publications

Early detection of ketoprofen-induced acute kidney injury in sheep as determined by evaluation of urinary enzyme activities

Early detection of ketoprofen-induced acute kidney injury in sheep as determined by evaluation of urinary enzyme activities

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

Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus)

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