ISSN:
1432-0843
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary 1. The concentration of methotrexate in whole blood, plasma and erythrocytes was measured in three patients receiving 250 mg methotrexate by continuous intravenous infusion over 12 h for different malignant diseases. 2. Methotrexate was measured using a double-antibody radioimmunoassay which facilitated drug monitoring for 1–2 weeks. 3. The concentration of methotrexate in plasma was much higher than that in whole blood and erythrocytes during the period of infusion, but this profile was reversed during the elimination phase. 4. The concentration in erythrocytes fell rapidly immediately after the infusion ended, but thereafter, in contrast to plasma levels, methotrexate concentrations in erythrocytes did not appear to decay during the elimination phase. In one patient the concentration/time profiles differed between treatment days. On the first occasion, at the initiation of chemotherapy, erythrocytes progressively accumulated methotrexate in the elimination phase against an apparent concentration gradient. On the second occasion this progressive increase was not observed, but as in the other two patients, methotrexate levels in red cells remained many times higher than drug levels in plasma throughout the period of observation. 5. Folinic acid administration did not appear to influence the distribution of methotrexate between red cells and plasma. 6. It was concluded that while the distribution between plasma and erythrocytes was probably mediated by complex mechanisms, the results were consistent with the erythrocyte mass behaving as a slowly exchanging kinetic compartment. Accumulation and persistence of a drug such as methotrexate in red cells might be expected to promote resistance and perhaps influence the expression of toxicity.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00265389
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