Mader R M, Steger G G, Moser K, Rainer H, Krenmayr P, Dittrich C
Department of Chemotherapy, University of Vienna, Austria.
Cancer Chemother Pharmacol. 1991;27(5):354-60. doi: 10.1007/BF00688857.
Degradation of etoposide is rapid under in vitro culture conditions. At pH 7.4 and 37 degrees C, the isomerisation of trans-etoposide to the inactive compound cis-etoposide has a half-life of 2 days in Dulbecco's modified Eagle's medium and results in the loss of 90% of the active drug within 1 week. As a consequence, prolonged incubations with etoposide in in vitro assays may lead to erroneous interpretations ignoring the real in vitro situation. The degradation is not influenced by organic compounds such as bovine serum albumin or amino acids but depends strongly on the pH value and, to a lesser degree, on the ionic strength of the medium. Therefore, we propose a mathematical correction based on the pH value so as to obtain the real exposure of cells to trans-etoposide during in vitro assays.
在体外培养条件下，依托泊苷降解迅速。在pH 7.4和37摄氏度时，反式依托泊苷异构化为无活性化合物顺式依托泊苷，在杜尔贝科改良伊格尔培养基中的半衰期为2天，1周内活性药物损失90%。因此，在体外试验中长时间用依托泊苷孵育可能会导致忽略实际体外情况的错误解读。降解不受牛血清白蛋白或氨基酸等有机化合物的影响，但强烈依赖于pH值，并在较小程度上依赖于培养基的离子强度。因此，我们提出基于pH值的数学校正方法，以便在体外试验中获得细胞对反式依托泊苷的实际暴露情况。
