Pharmacokinetics of CuDIPS in mice.
Pharmacokinetic evaluation of Cu(II)2(3,5-diisopropylsalicylate)4(H2O)2 (CuDIPS), a copper complex with anticancer activity in mice, showed rapid absorption into the circulation after subcutaneous (SC) injection of a 0.50mumol, 0.75 mumol or 1.0 mumol dose. A direct relationship was observed between peak plasma copper concentration (one or two hours) and dose. Rate of plasma release also appeared to be dose related. The lowest dose of CuDIPS had no effect on plasma zinc levels; higher doses produced significant increases, but only at one hour. Rapid absorption into the blood (apparent peak in concentration, Tmax, at 0.5 hours) was also found in studies to determine distribution of 67Cu after SC injection of 67Cu and 14C double-labeled CuDIPS (50 mumol/kg body weight). Distribution to other tissues and organs occurred less rapidly with apparent peak 67Cu concentrations at three hours after administration in femur (bone marrow) and intestine, and at six hours in spleen and thymus.
Crispens
C G
CG
Department of Biology, University of Alabama, Birmingham 35294.
Chidambaram
M V
MV
Torregrosa
D
D
Salari
H
H
Bond
K
K
Kearns
G L
GL
Gray
R A
RA
Epperson
C E
CE
Baker
M L
ML
Griffey
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D003300:Copper / Q000097:blood; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D012459:Salicylates / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015032:Zinc / Q000097:blood
D000970:Antineoplastic Agents; D012459:Salicylates; C030865:copper bis(3,5-diisopropylsalicylate); D003300:Copper; D015032:Zinc