This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lowenthal, I. S. Articles by Samy, T. S. A. Search for Related Content PubMed PubMed Citation Articles by Lowenthal, I. S. Articles by Samy, T. S. A.

Pharmacokinetic Analysis of Neocarzinostatin in Normal and Tumor-bearing Rodents¹

Sidney Farber Cancer Institute [I.S.L., L.M.P., B.L.B., T.S.A.S.] and Clinical Pharmacology Unit, Massachusetts General Hospital [D.J.G.], Harvard Medical School, Boston, Massachusetts 02115

Neocarzinostatin (NCS) is an acidic protein with proven antitumor activity in experimental animals and is now in clinical trial as a cancer chemotherapeutic agent. Utilizing a ¹²⁵I-labeled bisamino-modified derivative, the distribution, excretion, and metabolism of NCS have been studied in normal and tumor-bearing rodents.

NCS is rapidly excreted in the urine, with about 55% of the drug excreted unchanged in the first hr. About 10% of the radioactivity remained in the blood 1 hr after administration and was associated with peptides with molecular weights of 1500; these were not detected in the urine. The mean urinary excretion half-life of 1.65 hr was less than the apparent elimination half-life from blood (6.2 hr). Biliary excretion contributed little to the total clearance of NCS, since only a small fraction of the drug appeared unchanged in the bile. Although biliary excretion increased in the anephric rat, it proceeded at a maximum rate of 0.25 to 0.3%/hr. Tissue levels of ¹²⁵I-NCS were highest in kidney, the principal organ of excretion. Decreasing levels were observed in the skin, lung, intestine, pancreas, liver, spleen, muscle, thymus, and bone. ¹²⁵I-NCS was low in the testis and practically excluded from the brain. Radioactivity due to ¹²⁵I-NCS persisted in the Walker 256 ascites tumor in the rat but not in the ascites of the L1210 leukemia in mice. Since there is rapid elimination of the drug from the central compartment and little persistence in the tissues 6 hr after single (i.v.) injection, optimal scheduling may be frequent single injections or short continuous-flow infusions.

¹ This investigation was supported by National Cancer Institute Research Grants CA 17305 and CA 06516.

² Present address: Associated Internists of Danbury, Glenn Hill Rd., Danbury, Conn. 06810.

³ Supported by USPHS Grant MH-12279.

⁴ To whom requests for reprints should be addressed.

Received 5/17/78. Accepted 1/30/79.