[Studies of methotrexate pharmacokinetics in children with neoplasms of the hematopoietic system after administration of different doses of the drug]. / Badania farmakokinetyki metotreksatu u dzieci z nowotworami ukladu krwiotwórczego po podaniu róznych dawek tego leku.

Concentration of MTX was determined in the serum after the infusion of MTX in a dose of 0.5 g/m2, 1.0 g/m2 and 5.0 g/m2 to 24 children with ALL/NHL. The mean value of steady-state concentrations of MTX was two-fold greater after the infusion of a dose of 1.0 g/m2 and ten-fold greater after the infusion of a dose 5.0 g/m2 than at dose 0.5 g/m2. Great inpatient and interpatient variations of serum MTX concentrations were observed. Pharmacokinetic analysis of the data revealed biphasic model of the elimination. Statistically significant differences were found between the half-life MTX values (ti/2 alpha) in the first postinfusion day: the higher the dose, the shorter ti/2 was observed. The ti/2 of MTX during the second postinfusion day was significantly longer than that of the first day after infusion, but values for the higher doses were not significantly shorter than those for 0.5 g/m2. Systemic clearance (Cl) of MTX showed inpatient and interpatient variations of the values. However, no statistically significant difference was found between Cl values at doses of 0.5 g/m2, 1.0 g/m2 and 5.0 g/m2.

[Cerebrospinal fluid methotrexate level in children treated with medium-high and high doses of the drug]. / Stezenie metotreksatu w plynie mózgowo-rdzeniowym u dzieci leczonych srednio duzymi i duzymi dawkami leku.

Concentrations of MTX were determined in the cerebrospinal fluid (csf) and serum after intravenous infusion of MTX at intermediate dose (0.5-1.0 g/m2) and at high dose (5.0 g/m2) to 20 children (33 infusions) with ALL/NHL. The cytotoxic concentrations of MTX in csf (> 1.0 microM/l) were reached in half of the cases after the infusion of MTX at intermediate dose and in all patients after the infusion of 5.0 g/m2. Great inpatient and interpatient variations of MTX concentrations in csf were observed. No statistically significant difference was found between mean systemic clearance of MTX in patients with MTXcsf concentrations > 1.0 microM/l and < 1.0 microM/l after infusion of MTX at intermediate dose.