Effect of amoxicillin and cefalexin on the pharmacokinetics of diclofenac sodium in healthy volunteer

الملخص EN

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.