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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Maeda, H. Articles by Ogata, J. Search for Related Content PubMed PubMed Citation Articles by Maeda, H. Articles by Ogata, J.

 Previous Article  |  Next Article 

Antimicrob Agents Chemother. 1977 June; 11(6): 941-945
Copyright © 1977 American Society for Microbiology. All Rights Reserved.

Mechanism of Accumulation of the Antitumor Protein Antibiotic Neocarzinostatin in Bladder Tissue: Intravenous Administration, Urinary Excretion, and Absorption into Bladder Tissue

^* Department of Microbiology, Kumamoto University Medical School, Kumamoto, Japan 860
Department of Urology, Kumamoto University Medical School, Kumamoto, Japan 860

ABSTRACT

Some aspects of the absorption, distribution, and excretion of neocarzinostatin (NCS), a proteinous antitumor antibiotic, were studied in rabbits. NCS was given intravenously (i.v.) via the auricular vein, or [¹⁴C]NCS was instilled directly into the cavity of the bladder by tubing. In both groups, ureterostomy was performed, so that the drug excreted in the urine did not pass through the bladder. The results showed extremely rapid renal clearance; namely, two-thirds of the total recovered was excreted in the first 5 min. It was also shown that drug infused into the bladder cavity could be recovered in urine from the ureterostomized ureter. Also, the level of biological activity of NCS in bladder tissues after i.v. administration is significantly lower when ureterostomy is performed. Thus, evidence is presented for the absorption of NCS into bladder tissue from the lumen of the bladder. The high levels of NCS in bladder tissue are due to this effect as well as to accumulation via the iliac artery. These data should encourage further trials of NCS in bladder cancer. A study of urine containing NCS derived from i.v. administration showed an increase in antibacterial activity upon incubation, followed by a decrease. These effects are probably due to proteolysis, as shown by the appearance of a low-molecular-weight fragment and by the absence of such an increase in the presence of inhibitors of proteolysis.