Effect of sodium diclofenac on the bioavailability of amoxicillin

The aim of this study was to evaluate the effect of sodium diclofenac on the bioavailability of amoxicillin. In this randomised, crossover study with a 1-week washout period, 20 volunteers received a 2 g oral dose of amoxicillin (Amoxil®) (Group 1) or a 2 g oral dose of amoxicillin with 100 mg of sodium diclofenac (Voltaren®) (Group 2). Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 h following drug administration. High-performance liquid chromatography with ultraviolet detection was used to quantify plasma amoxicillin concentrations. Bioassay (Micrococcus luteus ATCC 9341) was performed to verify the antimicrobial efficacy of amoxicillin in vitro. The pharmacokinetic parameters area under the plasma concentration–time curve (AUC), maximum plasma concentration observed during the 24-h study period (Cmax) and renal clearance (CL) were analysed by analysis of variance, and time at which Cmax occurred (Tmax) and volume of distribution (VD) were analysed by Wilcoxon test (P < 0.05). For Group 1, the mean (± standard deviation) AUC0–24, Cmax and Tmax values were 3391.8 ± 1186.7 μg min/mL, 17.3 ± 6.5 μg/mL and 121.5 ± 20.6 min, respectively; and for Group 2, the values were 2918.4 ± 1024.8 μg min/mL, 15.5 ± 5.8 μg/mL and 136.5 ± 30.0 min, respectively. Lower values of AUC and Cmax were observed for Group 2 (P < 0.05). CL of amoxicillin increased (P < 0.05) by 18.5% in Group 2, suggesting that sodium diclofenac may interfere with amoxicillin renal excretion. In conclusion, sodium diclofenac can significantly reduce the bioavailability of amoxicillin.