PT  - JOURNAL ARTICLE
AU  - Felder, T B
AU  - McLean, M A
AU  - Vestal, M L
AU  - Lu, K
AU  - Farquhar, D
AU  - Legha, S S
AU  - Shah, R
AU  - Newman, R A
TI  - Pharmacokinetics and metabolism of the antitumor drug amonafide (NSC-308847) in humans.
DP  - 1987 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 773--778
VI  - 15
IP  - 6
4099  - http://dmd.aspetjournals.org/content/15/6/773.short
4100  - http://dmd.aspetjournals.org/content/15/6/773.full
SO  - Drug Metab Dispos1987 Nov 01; 15
AB  - 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 were administered 400 mg/m2 of drug as a 30-min infusion on a daily schedule for 5 consecutive days. Amonafide concentrations in plasma and urine were determined using reversed phase HPLC. Amonafide was eliminated from plasma with a terminal half-life of 3.5 hr. Renal excretion accounted for 23% of the administered dose. Amonafide pharmacokinetic parameters after the initial dose (day 1) were similar to those calculated after the fifth daily dose. Amonafide undergoes a significant amount of metabolism and eight urinary metabolites have been identified using a thermospray liquid chromatography-mass spectrometry (LC/MS) technique. Various N-acetylated species appear to be the major metabolites, although no evidence of N-acetylation was found in urine obtained from two patients. Two of the primary metabolites, the N(N5)-acetyl and N'(N1)-oxide metabolites of Amonafide, were tested in vitro for cytotoxicity against P388 murine leukemia cells. In this test system, the N-acetyl metabolite was observed to be only slightly less cytotoxic than the parent compound. The N'-oxide of Amonafide, however, proved to be inactive. These results are discussed together with the pharmacokinetic and metabolism data of this new investigational antitumor drug.