Pharmacokinetics and pharmacodynamics of (S)-ketoprofen co-administered with caffeine: a preclinical study in arthritic rats Abstract: The purpose of the present study was to determineing if 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 0.5-24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR model before blood sampling between 0.5-4.0 h. Significant differences in Cmax, AUC0-24 and AUC0-∞ values were observed with caffeine administration (p < 0.05). Also, Ssignificant differences in Emax, Tmax and AUC0-4 values were determined when comparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetics and pharmacodynamics data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between the …show more content…
Briefly, the cartridges were preconditioned by flushing with 2 mL of methanol and 1 mL of HPLC water. Separately, 50 µL of plasma sample plus 100 µL of an 85% phosphoric acid:water mixture (1:10) and 10 µL of internal standard solution (diclofenac at 100 µg/mL) were vortex mixeding. Then, samples were loaded into the cartridge and allowed to stand for 5 min, washed with 0.6 mL of a water:methanol mixture (95:5. v/v) and then dried under vacuum. The (S)-ketoprofen was eluted with 1 mL of an acetonitrile:methanol mixture (50:50, v/v) at a flow rate of 1 mL/min. The eluate was evaporated to dryness in a water bath at 37.0 ± 0.5 ᵒC under a gentle stream of nitrogen. The residue was reconstituted in 50 µL of mobile phase and 30 µL were injected onto the HPLC