Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin.
We report here the results of serial determinations of free-sulfhydryl, protein content and platinum levels in plasma of cancer patients following either cisplatin (cis-DDP, 3 patients, 60 mg/m2) or carboplatin (JM-8, 3 patients, 300 mg/m2) i.v. administration. After treatment with cis-DDP, significant platinum binding to plasma components with MW greater than 25 kD was observed; the ratio free-sulfhydryls/protein content decreased during the first two hours, returning to normal values at 24 hours after injection. In contrast, no evidence of platinum binding to plasma components with MW greater than 25 kD was noted after JM-8 i.v. administration, and the ratio free sulfhydryls/protein content did not change significantly after treatment. In vitro experiments show that at a molar ratio cis-DDP:JM-8 1:10, the two compounds bind to low MW thiols with the same kinetics. These data seems to suggest different interactions at the plasma level of these drugs, which may be correlated with their different toxicity.
Tosetti
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Servizio di Farmacologia Tossicologica, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Rocco
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M
Fulco
R A
RA
Chiara
S
S
Bruzzone
M
M
Campora
E
E
Esposito
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001798:Blood Proteins / Q000032:analysis*; D016190:Carboplatin; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy; D010984:Platinum / Q000097:blood*; D013438:Sulfhydryl Compounds / Q000097:blood*
D001798:Blood Proteins; D009944:Organoplatinum Compounds; D013438:Sulfhydryl Compounds; D010984:Platinum; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin