RESUMEN
Background: High-dose methotrexate (HD-MTX) therapy is widely implemented for leukemia, osteosarcoma, and lymphoma. Although various measures have been taken to avoid toxicity from high serum MTX concentrations, there are many cases of delayed elimination of MTX. Objective: We suspected that delayed elimination of serum MTX was caused by unknown interactions between MTX and concomitant drugs. Methods: Concerning concomitant drugs in the case of delayed elimination of MTX, we performed screening tests in 35 patients who had undergone HD-MTX therapy. We then investigated the risk factors for delayed MTX elimination in 94 patients with leukemia, lymphoma, or osteosarcoma retrospectively. Results: The percentages of concomitant use of Stronger Neo-Minophagen C (SNMC), a glycyrrhizin preparation, and vincristine were higher in the delayed group. The percentage of delayed MTX elimination in patients receiving HD-MTX therapy was 41%. Multiple logistic regression analysis revealed that the concomitant use of SNMC solely was a significant risk factor for delayed MTX (odds ratio = 12.20; 95% CI = 1.06-139.84). Conclusion and Relevance: Concomitant use of SNMC was shown to be related to delayed elimination of serum MTX, and our results suggested a previously unknown drug-drug interaction between MTX and SNMC.
Asunto(s)
Monitoreo de Drogas/métodos , Metotrexato/administración & dosificación , Metotrexato/sangre , Cisteína/administración & dosificación , Cisteína/sangre , Cisteína/uso terapéutico , Combinación de Medicamentos , Interacciones Farmacológicas , Femenino , Glicina/administración & dosificación , Glicina/sangre , Glicina/uso terapéutico , Ácido Glicirretínico/administración & dosificación , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/sangre , Ácido Glicirretínico/uso terapéutico , Humanos , Leucemia/sangre , Leucemia/tratamiento farmacológico , Modelos Logísticos , Linfoma/sangre , Linfoma/tratamiento farmacológico , Masculino , Tasa de Depuración Metabólica , Metotrexato/uso terapéutico , Osteosarcoma/sangre , Osteosarcoma/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Vincristina/administración & dosificación , Vincristina/sangre , Vincristina/uso terapéuticoRESUMEN
Environmental factors affecting human health are generally classified into physical, chemical and biological factors. In this review article, we focus on ultraviolet (UV) as a physical factor, heavy metals as a chemical factor and Japanese cedar pollens as a biological factor. Since we believe that progress based on both fieldwork research and experimental research is essential in hygiene study, we included the results of both the research approached. We first introduced the mechanism of development of and prevention of UV-mediated skin melanoma in our experimental research after showing our epidemiological research on UV-mediated DNA damage in humans. We then introduced our evaluation of toxicity and development of a remediation system in our experimental research on heavy metals after showing our fieldwork research for the monitoring of drinking water from wells in Asian countries. We finally introduced the results of pathogenic analysis of pollinosis in our clinical study. We would be very happy if young researchers would re-realize the importance of experimental research as well as epidemiological research in hygiene study.