Potential interaction and toxicity of concurrently administered gentamicin or cefotaxime with Paracetamol in rabbits

ABSTRACT

The effect of co-administration of paracetamol with either gentamicin or cefotaxime on the antibiotic blood level was investigated in rabbits. Serum creatinine level and the activities of serum alanine aminotransferase [ALAT] and aspartame aminotransferase [ASAT] were measured before and after 10 days of treatment in case of each combination. Also, the concentration of hemoglobin and the count of RBCs were determined before and after treatment. Body weight was monitored throughout the time of experiment. It was found that concurrent administration of paracetamol with gentamicin resulted in a significant increase in gentamicin level after 1, 2, 18 and 24 hours from drug administration. Similarly, blood level of cefotaxime was also significantly increased at 1, 2, 8 and 24 hours after drug administration. Serum creatinine was increased significantly after gentamicin treatment. However, such increase was not observed in case of treatment with gentamicin/paracetamol combination. Neither cefotaxime alone nor cefotaxime/paracetamol combination produced any significant change in serum creatinine. Concerning the effect on the activities of ALAT and ASAT, only the combinations of gentamicin/paracetamol and cefotaxime/paracetamol were found to produce significant increase, while single treatment with antibiotics did not produce any change. No change was observed in the blood parameters studied or in body weight. From this study, it was concluded that the use of paracetamol in combination with either gentamicin or cefotaxime is almost safe and the observed hepatic effect is mainly due to paracetamol. Also, with antibiotic, blood should be monitored if administered concurrently with paracetamol