title: L-histidinol: preclinical therapeutic studies in combination with antitumor agents and pharmacokinetic studies in mice.
abstract: Therapeutic studies were conducted with L-histidinol, in combination with cyclophosphamide, bischloroethylnitrosourea, 5-fluorouracil, phenylalanine mustard, or cis-platinum(II)diammine dichloride, in several transplantable tumors in mice. These tumor types included murine L1210 P388 leukemias, M5076 sarcoma, mammary 16/C adenocarcinoma, human LOX melanoma, and colon HT-29 adenocarcinoma. Therapeutic benefits of adding L-histidinol to a regimen, compared to the regimen alone, were marginal. Pharmacokinetic studies indicated a rapid clearance of L-histidinol following a bolus dose (250 mg/kg i.p.), peak plasma concentration of 200 micrograms/ml (1.4 mM), and beta phase t1/2 of 12.6 min. Maximum tolerable plasma steady state concentrations with a 24-h infusion (2000 mg/kg/24 h) were no greater than 25 micrograms/ml (0.18 mM).
authors.affiliation: Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: D
authors.initials: D
authors.lastname: Zaharko
authors.forename: J
authors.initials: J
authors.lastname: Plowman
authors.forename: W
authors.initials: W
authors.lastname: Waud
authors.forename: D
authors.initials: D
authors.lastname: Dykes
authors.forename: L
authors.initials: L
authors.lastname: Malspeis
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D006641:Histidinol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014183:Transplantation, Heterologous
chemical_list: D006641:Histidinol; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine