Pharmacokinetics of Methotrexate and 7-Hydroxy-Methotrexate After Methotrexate Infusions

Abstract

Methotrexate was administered by IV infusion, 2g (1.19 ± 0.05g/m²)over 24 hours, to a homogeneous group of patients undergoing treatment for breast cancer. Three courses were given at three week intervals.Methotrexate and 7-hydroxy-methotrexate plasma and urine pharmacokinetics were investigated. The average terminal half-lives of methotrexate and 7-hydroxy-methotrexate in plasma were 15.02 and 15.19 hours respectively. The area under concentration-time curve was 723.8 ± 196.4 uM x h for methotrexate and 598.1 ± 212.5 uM x h for 7-hydroxy-methotrexate. The total average urinary excretions of methotrexate and 7-hydroxy-methotrexate over a 96 hour period were 52% and 5.4% respectively. Urinary clearance of methotrexate was 3.46 ± 1.4 1/h. In contrast, urinary excretion of 7-hydroxy-methotrexate was not linear. These results confirm the protein binding of metabolite to serum albumin and may suggest that distribution of 7-hydroxy-methotrexate is different from unchanged drug or that the metabolite can be eliminated by another route, such as bile.