[Pharmacokinetics of neocarzinostatin in patients with malignant glioma. Quantitative analysis of tissue concentration].
Because of technical difficulties, the pharmacokinetics of neocarzinostatin (NCS) have not been thoroughly evaluated in patients with malignant glioma. The authors produced anti-NCS antibody by immunizing rabbits with NCS and established a means of quantifying tissue levels of NCS with enzyme-linked immunosorbent assay. In one patient given a bolus injection of 1 mg of NCS intra-arterially, the concentration of drug in neoplastic tissue at 25 minutes (0.1136 micrograms/g) was higher than that in blood at 20 minutes and was retained for a longer period. Rapid entry of NCS into the tumor cavity was observed at 5 minutes. In two postoperative cases, NCS applied topically to the tumor site (50 and 100 micrograms) was retained at high levels (0.2941 and 3.33 micrograms/ml) even after 48 hours, although no NCS was detected in blood after 60 minutes. NCS concentrations as low as 1 microgram/ml demonstrated cytocidal effects, and a delay in tumor growth was observed even at an NCS level of 0.1 microgram/ml, despite the fact that the half-life of NCS is extremely short (3 seconds in serum). Because its cytotoxic effect seems to be very rapid, it appears more important to obtain a high initial NCS concentration than to maintain a constant blood level.
Otsuka
T
T
Matsukado
Y
Y
Uemura
S
S
Kuratsu
J
J
Sonoda
H
H
Mihara
Y
Y
Goto
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D009353:Zinostatin / Q000493:pharmacokinetics* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D009353:Zinostatin