Motorização terapêutica do metotrexato sob altas doses, em pacientes portadores de leucemia linfoblástica aguda
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Data
2008-09-29
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Universidade Federal de Goiás
Resumo
Methotrexate (MTX) is a drug with high toxicity, used in high doses for the treatment of neoplasic diseases. Therapeutic concentrations preserve the effectiveness, but higher values increases the toxicity risks. The aim of this article was to develop and validate an analytical method on HPLC-PDA to measure methotrexate plasma levels on children affected by LLA. The analytical method was performed with a mobile
phase composed by acetic acid 0,1%:methanol:acetonitrile in concentration gradients during the analysis. The validation parameters were: specificity, relative recovery, lowest (LLQ) and higher limits of quantification, precision (Intra-assay standard deviation), accuracy, log time stability, calibration curve and co-validation. Biological samples were collected from 7 patients hospitalized on Araújo Jorge Hospital
totaling 42 blood samples used to estimate the pharmacokinetic parameters. As results we obtained a method with a flow-rate of 1.5 mL/min, the methotrexate and
teophyllin detection were observed in 304 and 271 nm respectively, in 13 minutes of carryover. The relative recovery was about 71%, LLQ about 0,1 μg/Ml. Intra-assay
standard deviation was 11% for LLQ and no more than 14,88% for other concentrations; the accuracy was 97,63% and the long time stability was confirmed in human blood with a -20º C freezing. As pharmacokinetic parameters, we estimate the total clearance (3,03 L/h), constant of elimination (0,2586 h-1), a distribution volume of 12,57 L, half-life time as 2,73 h and median AUCT (for area under the time vs concentratrion curve) of 626,493 μgh/mL. As conclusion, the analytical method proved to be high efficient to detect and to quantify the drug on human blood, and we observed the high variability of the pharmacokinetic parameters, showing the importance of realize the therapeutic drug monitoring.
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LELES, Raphael Nunes. Therapeutical drug monitoring of methotrexate under high dosages in pacients with acute lymphoblastic leukemia. 2008. 95 f. Dissertação (Mestrado em Ciências da Saúde - Farmácia) - Universidade Federal de Goiás, Goiânia, 2008.