Pharmacokinetics and metabolism of the antitumor drug amonafide (NSC-308847) in humans.

摘要: Pharmacokinetics and urinary excretion of Amonafide (5-amino-2-[2-(dimethylamine)ethyl]-1H-benz[de]isoquinoline-1,3-(2H)- dione) were examined in seven patients who administered 400 mg/m2 drug as a 30-min infusion on daily schedule for 5 consecutive days. concentrations plasma urine determined using reversed phase HPLC. was eliminated from with terminal half-life 3.5 hr. Renal accounted 23% the dose. pharmacokinetic parameters after initial dose (day 1) similar to those calculated fifth undergoes significant amount metabolism eight metabolites have been identified thermospray liquid chromatography-mass spectrometry (LC/MS) technique. Various N-acetylated species appear be major metabolites, although no evidence N-acetylation found obtained two patients. Two primary N(N5)-acetyl N'(N1)-oxide Amonafide, tested vitro cytotoxicity against P388 murine leukemia cells. In this test system, N-acetyl metabolite observed only slightly less cytotoxic than parent compound. The N'-oxide however, proved inactive. These results are discussed together data new investigational antitumor drug.