Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro |
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| Authors: | Eugen Musch Mouhamad Malek Jasna Peter-Katalinic Heinz Egge Hermann Rink Bernd Lathan Eberhard Riedel |
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| Affiliation: | (1) Department of Internal Medicine, Mary's Hospital Bottrop, FRG;(2) Department of Internal Medicine, University of Bonn, Sigmund-Freud-Str. 25, D-5300 Bonn 1, Federal Republic of Germany;(3) Institute for Physiological Chemistry, University of Bonn, FRG;(4) Institute for Radiobiology, University of Bonn, FRG;(5) Department of Internal Medicine, University of Cologne, FRG;(6) Institute for Biochemistry, University of Berlin, FRG |
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| Abstract: | Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen |
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