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Collagen Chemoembolization: Pharmacokinetics and Tissue Tolerance of cis-Diamminedichloroplatinum(II) in Porcine Liver and Rabbit Kidney¹

Kenneth Norris, Jr., Research Institute and Cancer Hospital, University of Southern California, Los Angeles 90033 [J. R. D.], and Target Therapeutics, Inc., Los Angeles, California 90025 [J. R. D., M. S., A. D.]

Pharmacokinetics of chemoembolization with a fibrous collagen carrier was studied in rabbit kidney and porcine liver models. Cisplatin (1 mg/ml) chemoembolization of liver and kidney was compared with i.v. and intraarterial cisplatin infusion. Tissue platinum concentration [Pt] was measured at 2.5 h by atomic absorption spectrometry. Renal platinum retention and Angiostat (collagen for embolization) concentration were linearly related (r = 0.87, p < 0.001). At 10 mg/ml collagen for embolization, chemoembolized kidney [Pt] was 220 ± 50 (SE; n = 4) times contralateral kidney [Pt], and 62 and 23 times renal [Pt] by i.v. and intraarterial infusion, respectively. At 10 mg/ml collagen for embolization, chemoembolized liver [Pt] was 2 times hepatic [Pt] by i.v. and intraarterial infusion. Since hepatic tumor vasculature is end arterial, chemoembolization should yield high [Pt] in tumor (as in kidney) but lower levels in normal liver.

¹ Supported in part by Bristol Myers Company, Collagen Corporation, and Eli Lilly Company.

² To whom requests for reprints should be addressed, at 2100 S. Sepulveda Boulevard, Los Angeles, CA 90025.

Received 6/24/87. Revised 12/ 1/87. Accepted 1/27/88.

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