Disposition of DX-52-1, a novel anticancer agent, after intravenous administration to mice and dogs.
DX-52-1 is a new derivative of a quinocarmycin analogue. The disposition of [3H]-DX-52-1 was investigated in mice and dogs after intravenous administration (4 and 0.15 mg/kg, respectively). The plasma concentration of non-volatile radioactivity was 7.4 micrograms eq./ml 3 min after administration to mice, then declined biphasically until 2 h. The distribution of non-volatile radioactivity into blood cells was 20% 3 min after administration, being maintained until 30 min. The plasma concentration of unchanged drug was almost equal to that of the radioactivity 3 min after administration and the unchanged drug ratio decreased rapidly. High radioactivity was found in the gall bladder, kidney, liver, and lung 15 min after administration. No radioactivity was detected in most tissues 24 h post-administration. The cumulative excretion of total radioactivity into urine and feces after administration was 68 and 28% within 96 h, respectively. The plasma concentration of non-volatile radioactivity was 0.65 micrograms eq./ml 3 min after administration to dogs. The distribution of non-volatile radioactivity into blood cells was about 20% 3 min after administration and this level tended to increase with time. The cumulative excretion of total radioactivity into urine and feces after administration was 62 and 24%, respectively.
Fuse
E
E
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan.
Nishiie
H
H
Kobayashi
H
H
Ikeda
S
S
Saito
H
H
Covey
J
J
Kobayashi
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004285:Dogs; D005243:Feces / Q000737:chemistry; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution; D014316:Tritium / Q000097:blood / Q000652:urine
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; D014316:Tritium; C091971:DX 52-1