The kinetics and mechanisms of the reaction of Mesna with cisplatin, oxiplatin and carboplatin.
BACKGROUND
Mesna is a sulfohydrate administered as a supportive drug in conjunction with oxazaphosphorines to prevent bladder toxicity from metabolites. When oxazaphosphorines are given simultaneously with platinum drugs, Mesna binds with platinum drugs as well. Previously we showed in cell culture, that Mesna reduces the efficacy of some platinum drugs. Here we elucidate the chemical reaction mechanism.


METHODS
Cisplatin, Carboplatin and a novel platinum agent Oxiplatin were incubated with Mesna and the rate of disappearance of Mesna was measured, using an oxidation/reduction reaction between MTT and Mesna.


RESULTS
All three platinum agents reacted with Mesna, but the chemical details differed largely. The molar ratios were 3:1, 2:1, and 1:1 for the reactions of Mesna with Oxiplatin, Cisplatin, and Carboplatin, respectively. The speed of the reaction followed a similar pattern, being fastest for Oxiplatin and slowest for Carboplatin.


CONCLUSIONS
When considering the pharmacokinetics of Mesna and these platinum compounds and their reactivity, it appears unlikely that the reaction of Mesna with Carboplatin will become clinically relevant, while Cisplatin, might react with Mesna in patient serum.
Oprea
A
A
Cancer Biology Research Group, University of Calgary, Faculty of Medicine, Southern Alberta Cancer Research Centre, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
Bazzazi
H
H
Kangarloo
B
B
Wolff
J E
JE
D000970:Antineoplastic Agents / Q000737:chemistry*; D002138:Calibration; D016190:Carboplatin / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D007700:Kinetics; D015080:Mesna / Q000737:chemistry*; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry*; D017671:Platinum Compounds / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D011725:Pyridines; C431073:oxiplatin; D016190:Carboplatin; D015080:Mesna; D002945:Cisplatin