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Pharmaceutics 2018, 10(1), 20;

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

Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico
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
Author to whom correspondence should be addressed.
Received: 31 October 2017 / Revised: 16 January 2018 / Accepted: 23 January 2018 / Published: 26 January 2018
(This article belongs to the Special Issue Preclinical Pharmacokinetics and Bioanalysis)
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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 Cmax, AUC0-24, and AUC0-∞ values were observed with caffeine administration (p < 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 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 Emax model, a satisfactory correlation was found (R2 > 0.99) as well as significant differences in Emax and EC50 values (p < 0.05). With caffeine, Emax and EC50 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. View Full-Text
Keywords: (S)-ketoprofen; caffeine; pharmacokinetics; pharmacodynamics; PIFIR model (S)-ketoprofen; caffeine; pharmacokinetics; pharmacodynamics; PIFIR model

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Medina-López, R.; Vara-Gama, N.; Soria-Arteche, O.; Moreno-Rocha, L.A.; López-Muñoz, F.J. Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats. Pharmaceutics 2018, 10, 20.

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