Pharmacokinetics and Adverse Reaction in Methotrexate Therapy of Osteosarcoma.

Abstract

The effect of the dosage of methotrexate (MTX) on pharmacokinetic parameters in renal, hepatic and hematological functions were investigated. Twenty osteosarcoma patients (age: 13-53 years) received MTX infusions (dosage: 3.3-11.2g/m2) for 6 hrs. The serum MTX concentrations at 6h, 12h and 24h increased almost proportionally with the infused dose. The total serum MTX clearance and half-lives were almost constant in all the dosing ranges examined.To evaluate the relationship between the dosage and laboratory values, the patients were divided into three groups based on the MTX dosage and consisting of: low-dose (dosage: 3.3-5.2g/m2), middle-dose (dosage: 5.4-8.3g/m2), and high-dose (dosage: 9.0-11.2g/m2) groups. There was no significant difference between the renal and hematological functions before MTX infusion. In the high-dose group, significantly increased GOT and GPT values were observed on days 2 and 7, which indicate a decreased in hepatic function.In spite of the linear pharmacokinetics of MIX, a high-dose may cause remarkably nonlinear increased GOT and GPT values compared to those with low-and middle-doses.To avoid a severe adverse reaction of MTX therapy in the high-dosage group, careful monitoring of both the serum concentration of MTX and the liver functions is considered to be important after infusion.