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  • Title: L-histidinol: preclinical therapeutic studies in combination with antitumor agents and pharmacokinetic studies in mice.
    Author: Zaharko D, Plowman J, Waud W, Dykes D, Malspeis L.
    Journal: Cancer Res; 1992 Jul 01; 52(13):3604-9. PubMed ID: 1617631.
    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).
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