The kinetics and cytotoxicity of cisplatin and its monohydrated complex.
This paper examines the monohydrated complex of cisplatin (MHC) with respect to kinetics and cytotoxicity. Equilibrium mixtures of cisplatin and hydrated species have been used in previous studies of a similar nature. To our knowledge, this is the first paper examining MHC after isolation and quantification. This was accomplished using liquid chromatography with porous graphitic carbon. MHC and cisplatin were quantified over time in a suspension of the small-cell lung cancer cell line U-1285. Cytotoxicity was evaluated using the fluorescent microculture cytotoxicity assay. MHC was significantly more cytotoxic than cisplatin at the high end of the drug concentrations tested. In culture media with low chloride ion concentrations, the stability of MHC was related to changes in pH. At a pH of between 6.0 and 7.2, MHC was rapidly converted to cisplatin. In culture media with a pH above 7.2, MHC was considerably more stable. These findings might have clinical significance given that MHC circulates in the blood stream of patients receiving cisplatin infusions and that solid tumours often have environments that are extremely acidotic.
Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
J R
JR
Yachnin
I
I
Wallin
R
R
Lewensohn
F
F
Sirzén
H
H
Ehrsson
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D003470:Culture Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D018675:Toxicity Tests; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D003470:Culture Media; D002945:Cisplatin