Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats.

Autor: Medina-López R; Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico. rmlopez@correo.xoc.uam.mx., Vara-Gama N; Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico. inukiniro@yahoo.com.mx., Soria-Arteche O; Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico. soriao@correo.xoc.uam.mx., Moreno-Rocha LA; Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico. alfonso.moreno72@gmail.com., López-Muñoz FJ; Laboratorio No. 7 'Dolor y Analgesia' del Departamento de Farmacobiologia, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235, Col. Granjas Coapa, Mexico City 14330, Mexico. flopezm2@gmail.com.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2018 Jan 26; Vol. 10 (1). Date of Electronic Publication: 2018 Jan 26.
DOI: 10.3390/pharmaceutics10010020
Abstrakt: The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of ( S )-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of ( S )-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in C max , AUC 0-24 , and AUC 0-∞ values were observed with caffeine administration ( p < 0.05). Also, significant differences in E max , T max , and AUC 0-4 values were determined when comparing the treatments with and without caffeine ( p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal E max model, a satisfactory correlation was found (R² > 0.99) as well as significant differences in E max and EC 50 values ( p < 0.05). With caffeine, E max and EC 50 values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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