Alterations in plasma pharmacokinetics of cisplatin in tumor-bearing rats.
Rats were inoculated s.c. with the Walker 256 solid carcinosarcoma, and when tumors reached a weight of approximately 2-3 g, pharmacokinetics, tissue distribution, and urinary excretion of 195mPt-labelled cisplatin were studied. Cisplatin was given i.v., blood was sampled through arterial cannulae, and data were fitted to a three-compartment model. Distribution half-times were prolonged two- to threefold in tumor-bearing animals, although there was no change in elimination half-time. Initial and steady-state volumes of distribution were also increased in tumor-bearing animals. There was no change in AUC, urinary excretion, tissue distribution, or plasma protein binding. The results indicate that a solid tumor represents an additional compartment for distribution of cisplatin and alters the rate at which cisplatin is distributed from the plasma.
Litterst
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Laboratory of Biochemical Pharmacology, National Cancer Institute, Bethesda, MD 20892.
Magin
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D000818:Animals; D002279:Carcinoma 256, Walker / Q000097:blood / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood; D002945:Cisplatin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D010984:Platinum / Q000097:blood; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D002352:Carrier Proteins; D010984:Platinum; D002945:Cisplatin