title: Relationship between blood levels and the anti-hyperalgesic effect of ketoprofen in the rat.
abstract: 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.
authors.affiliation: Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, México, D.F., 11000, México.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Aguilar-Carrasco
authors.forename: Juan
authors.initials: J
authors.lastname: Rodríguez-Silverio
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Jiménez-Andrade
authors.forename: Miriam del Carmen
authors.initials: Mdel C
authors.lastname: Carrasco-Portugal
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Flores-Murrieta
mesh_terms: D000700:Analgesics / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D002351:Carrageenan; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D007660:Ketoprofen / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D002351:Carrageenan; D007660:Ketoprofen
keywords: analgesia; ketoprofen; pharmacokinetics