Effect of Amoxicillin And Cefalexin on The Pharmacokinetics of Diclofenac Sodium in Healthy Volunteers

Abstract

Background: Studies investigating the effect of antibiotics on the pharmacokinetics of non-steroidal anti-inflammatory drugs are few. Such interaction could be clinically significant in conditions like diabetic nephropathy. Objectives: To study the effect of amoxicillin and cefalexin on the pharmacokinetics of diclofenac sodium when taken concomitantly. Subjects and Methods: Eleven healthy subjects participated in this single dose cross-over study. Each volunteer randomly joined one of the three treatment groups and received a single dose of diclofenac sodium (50mg enteric-coated tablet), diclofenac sodium + amoxicillin 500mg capsule, and diclofenac sodium + cefalexin 500mg capsule successively with one week washout interval. Blood samples were taken immediately before, at 30 minutes and at 1, 1.5, 2, 2.5, 3, 4 and 6 hours after drug administration and analyzed using high performance liquid chromatography (HPLC) system with ibuprofen as internal standard. Results: Diclofenac sodium produced a maximum concentration of 1.34 µg/ml with a half life of 0.5 hour and area under plasma concentration versus time curve up to 6 hours (AUC0-6) of 1.24 µg.h/ml. Although the AUC0-6 and maximum plasma concentration of diclofenac sodium increased by more than 20% after co-administration of amoxicillin, this increase is not statistically significant. Cefalexin, on the other hand, when given with diclofenac sodium significantly increased the AUC0-6 and maximum plasma concentration of diclofenac by 51.9% and 68.5% respectively. Conclusion: Amoxicillin and cefalexin can change some of the pharmacokinetic parameters of diclofenac tablet when administered concomitantly and cefalexin did that to a greater extent. Such interaction must, therefore, be considered in conditions where diclofenac might be harmful.