Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

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Elevated homocysteine concentrations have Eyewear Lens Cleaning been associated with methotrexate-induced neurotoxicity.Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD) model was built with NONMEM.Several compartment and indirect response models were investigated.The pharmacokinetic disposition of methotrexate was best described by a two-compartment model.

Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by SHOWER PURIFIER #360 an E(max) model.The homocysteine baseline level was found to be age-dependent.Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure.In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.