[Study on the intra-tumor tissue concentration of zinostatin stimalamer in the liver following intra-arterial injection of zinostatin stimalamer (YM881) suspension].
A suspension of zinostatin stimalamer (YM881), an antitumor protein antibiotic in iodized poppy oil-fatty acid ester, was injected into the hepatic artery of 2 patients who received surgical treatment of hepatic tumors. Single doses of 4 mg of zinostatin stimalamer were injected into the hepatic artery by Seldinger's method. Two and 4 weeks after the dose, tissue samples were collected from the tumor and non-tumor regions close to and distant (normal tissues) from the tumor, and zinostatin stimalamer concentrations in these tissues were assayed by RIA. In one of the two patients, plasma concentrations of the drug were also assayed. Concentrations of zinostatin stimalamer in the tumor tissues (381.8 ng/g) were about 55 times greater than those in the normal tissue (6.9 ng/g) in patient No. 1 (week 4), and about 17 times in patients No. 2 (13.9 ng/g in the normal tissue and 229.8 ng/g in the tumor tissues in week 2). Plasma concentrations were assayed in patient No. 2, and were 510.3 ng/ml after one hr., 385.3 ng/ml after 3 hrs., 184.4 ng/ml after 6 hrs., and 45.4 ng/ml after 24 hrs., with a half life of 7.1 hrs. These results indicate that zinostatin stimalamer suspended in iodized poppy oil fatty acid ester persisted in the hepatic tumor tissues at the high concentrations, when injected into the hepatic artery, but was eliminated fairly rapidly from the plasma.
Toge
T
T
Dept. of Surgery, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Japan.
Jinushi
K
K
Sawamura
A
A
Matsuki
K
K
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008299:Maleic Anhydrides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D011137:Polystyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009353:Zinostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D009353:Zinostatin