title: Clinical pharmacology of the anticancer polypeptide neocarzinostatin.
abstract: The clinical pharmacology of the anticancer polypeptide neocarzinostatin was studied in 16 patients with disseminated neoplasia using a radioimmunoassay technique. Patients who received 2,400-3,600 U of the drug per square meter BSA by rapid IV infusion had triphasic plasma decay curves. For eight patients with normal hepatic and renal function, neocarzinostatin mean plasma half-lives were 0.14, 0.50, and 7.7 h. The mean plasma drug clearance was 32.4 ml/min/m2 and the apparent volume of distribution 19.3 l/m2. Two patients with liver dysfunction had shorter terminal plasma half-lives and greater drug clearance, while two with renal disease exhibited prolonged plasma half-lives and reduced drug clearances. The mean cumulative urinary excretion of neocarzinostatin was 69.1% of the administered dose at 72 h in three patients with normal hepatic and renal function. One patient with liver disease excreted 90.4%, while a patient with renal disease excreted only 58.1% of the dose in 24 h. In one patient with marked liver disease, biliary excretion accounted for 0.1% of the administered dose in 72 h. Cerebrospinal fluid concentrations of neocarzinostatin studied in two patients showed a CSF penetration of about 16% the plasma concentration at 1-5 h; concentrations persisted for 19 h in one patient with an Omayha reservoir. Neocarzinostatin was rapidly cleared from the plasma and eliminated in the urine. Dosage reductions of 50% are recommended for patients with impaired renal function, while no reduction or escalated doses could be tolerated by patients with liver disease. The pharmacologic data suggest a continuous IV infusion may be a more toxic but perhaps more effective schedule of administration.
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011863:Radioimmunoassay; D014018:Tissue Distribution; D009353:Zinostatin / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000903:Antibiotics, Antineoplastic; D009353:Zinostatin