[A pharmacokinetic study on high-dose methotrexate administration--the effects of volume changes of parenteral solutions on the elimination rate].
Methotrexate (MTX) serum concentrations were measured in 7 cases (2 patients) in which a high-dose administration of MTX with citrovorum factor rescue for osteogenic sarcoma were performed for repressing activity in the original lesion and satellite micrometastasis. In the pharmacokinetic analysis, the changes of MTX serum concentrations were explained by a 2-compartment open model under the assumption that the elimination rate was proportional to both of volume of parenteral solution and the amount of water intake. It was suggested that MTX serum concentration could be controlled by adjusting the volumes of parenteral solutions. MTX amount in the peripheral compartment was found about ten times larger than that in the central compartment after about 40 h of administration. It is considered that an early increase in the volumes of parenteral solutions is effective to keep the safety level of MTX serum concentration, and continuous infusion is important for avoiding the severe side effects caused by delayed elimination of MTX.
Yoshioka
S
S
Hospital Pharmacy, Kagawa Medical School.
Tsukamoto
T
T
Nakano
M
M
Oka
S
S
Nakano
M
M
Norimatsu
H
H
D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008433:Mathematics; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*
D008727:Methotrexate