Relationship Between Blood Levels and the Anti-Hyperalgesic Effect of Ketoprofen in the Rat
Article first published online: 21 JAN 2014
© 2014 Wiley Periodicals, Inc.
Drug Development Research
Volume 75, Issue 3, pages 189–194, May 2014
How to Cite
Aguilar-Carrasco, J. C., Rodríguez-Silverio, J., Jiménez-Andrade, J. M., Carrasco-Portugal, M. d. C. and Flores-Murrieta, F. J. (2014), Relationship Between Blood Levels and the Anti-Hyperalgesic Effect of Ketoprofen in the Rat. Drug Dev. Res., 75: 189–194. doi: 10.1002/ddr.21167
- Issue published online: 9 MAY 2014
- Article first published online: 21 JAN 2014
- Manuscript Accepted: 17 DEC 2013
- Manuscript Received: 9 NOV 2013
The relationship between blood levels of ketoprofen and its anti-hyperalgesic effects was examined in rat using the carrageenan-evoked thermal hyperalgesia model. Female adult Wistar rats were injected with carrageenan into the plantar surface of the right hind paw. Immediately after, rats were administered with ketoprofen po and hindpaw withdrawal latency measured and micro-whole blood samples were obtained over six hours via a cannula inserted in the caudal artery. Ketoprofen levels were measured by HPLC. Ketoprofen concentration increased in a dose-dependent manner and was reflected in dose-dependent anti-hyperalgesic effect. The pharmacokinetic and pharmacodynamic parameters expressed as mean ± s.e.m. following administration of 1, 3.2, and 10 mg/kg ketoprofen were: Cmax 1.27 ± 0.08, 3.44 ± 0.20 and 11.76 ± 0.81 μg/mL; AUClast 4.16 ± 0.17, 11.63 ± 0.65 and 28.15 ± 1.32 μg h/mL; and Emax observed (AUCE): 65.41 ± 7.79, 92.06 ± 6.46 and 98.42 ± 7.53%. A direct relationship between blood concentrations and the anti-hyperalgesic effect of ketoprofen followed a maximum effect model equation. The results indicate that the anti-hyperalgesic effect of ketoprofen in the carrageenan pain model can be predicted by the pharmacokinetic properties of ketoprofen.