Study on the interaction between methotrexate and evetiracetam in rats / 中国药理学通报

ABSTRACT

Aim Study the interaction between metho-trexate and levetiracetam after oral administration and hepatorenal toxicity in rats, to provide theoretical basis for the clinical rational use of two drugs. Methods Male SD rats ( 250 ± 20 ) g were selected as experi-mental animals. Rats were randomly divided into 3 groups ( 1 mg·kg-1methotrexate group, 180 mg· kg-1 levetiracetam group, combined group), 5 rats in each group. The following experiment was carried out(1) pharmacokinetic parameters study; (2) renal ex-cretion study; (3) liver and kidney toxicity study. All samples were determined by ultra performance liquid chromatography-tandem mass spectrometry ( UPLC/MS/MS) . Results After the combination of two drugs, the Cmax, AUC0-t and Tmax of methotrexate in-creased, T1/2, Cl and MRT of methotrexate decreased, the differences was statistically significant. The Tmax, T1/2, Cl, MRT of levetiracetam had a certain upward trend, AUC0-t had a certain downward trend, the differences has no statistically significant. After combi-nation of two drugs, the renal excretion of methotrexate increased significantly, the renal excretion of levetirac-etam decreased significantly and hepatorenal toxicity increased significantly. Conclusion After combina-tion of two drugs by oral administration, Levetiracetam significantly increased methotrexate absorption in rats. Levetiracetam increased the plasma concentration and renal excretion of methotrexate and caused hepatorenal toxicity significantly. It is suggested that dose adjust-ment is necessary for combination of two drugs.