Relationship Between Serum Concentration at 48 h and Pharmacokinetic Characteristics and Toxic Reactions at Terminal Elimination Phase After Starting High Dose Methotrexate Infusion / 医药导报

ABSTRACT

Objective To recheck the reliability of methotrexate ( MTX) serum concentration at 48 h ( C48 h ) in predicting the pharmacokinetic characteristics and toxic reactions at terminal elimination phase after high dose MTX infusion and to provide a reference for determination of rational rescue regimen in clinic practice. Methods In total,114 cases of children with acute lymphoblastic leukemia (ALL) received 176 courses of high dose MTX chemotherapy treatment. The regimen was continuous infusion of MTX[3 -5 g·( m2 ) -1 ] in 24 h. Plasma samples were treated with solid phase extraction and serum concentrations of MTX were determined by HPLC at 24,48 and 72 h (C24 h ,C48 h and C72 h ) after starting MTX infusion. All data were divided into C48 h≥1 μmol·L-1 group and C48 h<1 μmol·L-1 group. The pharmacokinetic parameters of the two groups at elimination phase were estimated by residual method and the toxic reactions after MTX infusion of two groups were compared by Ridit analysis. Results The C72 h and AUC48-∞ were significantly higher in C48 h ≥1 μmol · L-1 group than in C48 h <1 μmol·L-1 group (P<0. 01). The MTX toxicities to the blood,digestive and hepatic systems were significantly higher in C48 h≥1 μmol·L-1 group than in C48 h < 1 μmol · L-1 group ( P < 0. 05). Conclusion C48 h can predict the pharmacokinetic characteristics and toxic reactions at ther terminal elimination phase. Therefore,C48 h≥1 μmol·L-1 can be used as a marker of MTX elimination delay event to guide later rescue regimen.