Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics
The non-steroidal anti-inflammatory drug ketoprofen (KTP) was administered as the racemate to cats intravenously (IV) and orally at clinically recommended dose rates of 2 and 1 mg/kg, respectively, to establish its chiral pharmacokinetic and pharmacodynamic properties. After IV dosing, clearance...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English Malay |
| Published: |
Elsevier Science
2003
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/6972/ http://psasir.upm.edu.my/id/eprint/6972/1/Ketoprofen%20in%20the%20Cat.pdf |
| _version_ | 1848840466738446336 |
|---|---|
| author | Lees, Peter Taylor, Polly Monroe Landoni, Maria Fabiana Abdul Kadir, Arifah Waters, C. |
| author_facet | Lees, Peter Taylor, Polly Monroe Landoni, Maria Fabiana Abdul Kadir, Arifah Waters, C. |
| author_sort | Lees, Peter |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | The non-steroidal anti-inflammatory drug ketoprofen (KTP) was administered as the racemate to cats intravenously (IV) and orally at clinically recommended dose rates of 2 and 1 mg/kg, respectively, to establish its chiral pharmacokinetic and pharmacodynamic properties.
After IV dosing, clearance was more than five times greater and elimination half-life and mean residence time were approximately three times shorter for R(−) KTP than for S(+) KTP. Absorption of both S(+) and R(−) enantiomers was rapid after oral dosing and enantioselective pharmacokinetics was demonstrated by the predominance of S(+) KTP, as indicated by plasma AUC of 20.25 (S(+)KTP) and 4.09 (R(−)KTP) μg h/mL after IV and 6.36 (S(+)KTP) and 1.83 (R(−)KTP) μg h/mL after oral dosing. Bioavailability after oral dosing was virtually complete. Reduction in ex vivo serum thromboxane (TX)B2 concentrations indicated marked inhibition of platelet cyclo-oxygenase (COX)-1 for 24 h after both oral and IV dosing and inhibition was statistically significant for 72 h after IV dosing. Both oral and IV rac-KTP failed to affect wheal volume produced by intradermal injection of the mild irritant carrageenan but wheal skin temperature was significantly inhibited by IV rac-KTP at some recording times. Possible reasons for the disparity between marked COX-1 inhibition and the limited effect on the cardinal signs of inflammation are considered.
In a second experiment, the separate enantiomers of KTP were administered IV, each at the dose rate of 1 mg/kg. S(+)KTP again predominated in plasma and there was unidirectional chiral inversion of R(−) to S(+)KTP. Administration of both enantiomers again produced marked and prolonged inhibition of platelet COX-1 and, in the case of R(−)KTP, this was probably attributable to S(+)KTP formed by chiral inversion.
|
| first_indexed | 2025-11-15T07:27:48Z |
| format | Article |
| id | upm-6972 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English Malay |
| last_indexed | 2025-11-15T07:27:48Z |
| publishDate | 2003 |
| publisher | Elsevier Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-69722015-10-06T00:53:24Z http://psasir.upm.edu.my/id/eprint/6972/ Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics Lees, Peter Taylor, Polly Monroe Landoni, Maria Fabiana Abdul Kadir, Arifah Waters, C. The non-steroidal anti-inflammatory drug ketoprofen (KTP) was administered as the racemate to cats intravenously (IV) and orally at clinically recommended dose rates of 2 and 1 mg/kg, respectively, to establish its chiral pharmacokinetic and pharmacodynamic properties. After IV dosing, clearance was more than five times greater and elimination half-life and mean residence time were approximately three times shorter for R(−) KTP than for S(+) KTP. Absorption of both S(+) and R(−) enantiomers was rapid after oral dosing and enantioselective pharmacokinetics was demonstrated by the predominance of S(+) KTP, as indicated by plasma AUC of 20.25 (S(+)KTP) and 4.09 (R(−)KTP) μg h/mL after IV and 6.36 (S(+)KTP) and 1.83 (R(−)KTP) μg h/mL after oral dosing. Bioavailability after oral dosing was virtually complete. Reduction in ex vivo serum thromboxane (TX)B2 concentrations indicated marked inhibition of platelet cyclo-oxygenase (COX)-1 for 24 h after both oral and IV dosing and inhibition was statistically significant for 72 h after IV dosing. Both oral and IV rac-KTP failed to affect wheal volume produced by intradermal injection of the mild irritant carrageenan but wheal skin temperature was significantly inhibited by IV rac-KTP at some recording times. Possible reasons for the disparity between marked COX-1 inhibition and the limited effect on the cardinal signs of inflammation are considered. In a second experiment, the separate enantiomers of KTP were administered IV, each at the dose rate of 1 mg/kg. S(+)KTP again predominated in plasma and there was unidirectional chiral inversion of R(−) to S(+)KTP. Administration of both enantiomers again produced marked and prolonged inhibition of platelet COX-1 and, in the case of R(−)KTP, this was probably attributable to S(+)KTP formed by chiral inversion. Elsevier Science 2003-01 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/6972/1/Ketoprofen%20in%20the%20Cat.pdf Lees, Peter and Taylor, Polly Monroe and Landoni, Maria Fabiana and Abdul Kadir, Arifah and Waters, C. (2003) Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics. The Veterinary Journal, 165 (1). pp. 21-35. ISSN 1090-0233 http://dx.doi.org/10.1016/S1090-0233(02)00168-5 10.1016/S1090-0233(02)00168-5 Malay |
| spellingShingle | Lees, Peter Taylor, Polly Monroe Landoni, Maria Fabiana Abdul Kadir, Arifah Waters, C. Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics |
| title | Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics |
| title_full | Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics |
| title_fullStr | Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics |
| title_full_unstemmed | Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics |
| title_short | Ketoprofen in the Cat: Pharmacodynamics and Chiral Pharmacokinetics |
| title_sort | ketoprofen in the cat: pharmacodynamics and chiral pharmacokinetics |
| url | http://psasir.upm.edu.my/id/eprint/6972/ http://psasir.upm.edu.my/id/eprint/6972/ http://psasir.upm.edu.my/id/eprint/6972/ http://psasir.upm.edu.my/id/eprint/6972/1/Ketoprofen%20in%20the%20Cat.pdf |