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A comparative study on the pharmacokinetics of methotrexate in a dose range of 0.5 g to 33.6 g/m 2 in children with acute lymphoblastic leukemia
Author(s) -
Borsi Joseph D.,
Moe Peter Johan
Publication year - 1987
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19870701)60:1<5::aid-cncr2820600103>3.0.co;2-d
Subject(s) - methotrexate , pharmacokinetics , volume of distribution , medicine , cerebrospinal fluid , acute lymphocytic leukemia , dose , distribution (mathematics) , pharmacology , lymphoblastic leukemia , leukemia , gastroenterology , mathematical analysis , mathematics
Concentrations of methotrexate have been determined in the serum and cerebrospinal fluid after 406 infusions of methotrexate to 58 children with acute lymphoblastic leukemia. The dose of methotrexate varied between 500 mg/m 2 and 33 600 mg/m 2 . Pharmacokinetic analysis of the data has been carried out. The effect of dose, age, and number of treatments on steady‐state concentration, serum half‐life, cerebrospinal fluid (CSF) serum distribution ratio, volume of distribution, systemic clearance of methotrexate was examined. The elevation of dose resulted in a nonproportional increase of the steady‐state concentrations both in serum and CSF. The great inpatient and interpatient variations of steady‐state concentrations caused only statistically not significant differences in the parameters of different subgroups of dosages. Correlation was found between concentrations of methotrexate in serum and CSF. One to 4 years old children were found to have lower steady‐state concentrations of methotrexate in the serum and CSF, greater volume of distribution and faster clearence of the drug. Dose‐dependency and age‐dependency of methotrexate pharmacokinetics has been concluded.