Pharmacokinetic analysis of in vivo disposition of heparin-superoxide dismutase.
To improve the half-life and tissue targeting of SOD to suppress reactive oxygen species (ROS)-mediated injury, chemically modified derivative of superoxide dismutase (SOD) with heparin, anionized SOD (Hep-SOD), was designed. In this study, the pharmacokinetics of Hep-SOD had been studied. This study aimed to investigate the pharmacokinetics, tissue distribution and cell targeting. ¹²⁵I-radiolabeled Hep-SOD conjugate was administered to healthy mice by intravenous (i.v.) bolus injection. Compared with native SOD, the half-life of Hep-SOD conjugate, including t(₁/₂α) and of t(₁/₂β), was lengthen and area under the plasma concentration versus time curve (AUC) of Hep-SOD was increased. The study showed that both native SOD and Hep-SOD was rapidly and widely distributed in the livers, kidneys, spleens, hearts and lungs. Furthermore, compared with Hep-SOD, radioactivity of native SOD decreased more sharply over time in most tissues. Compared with native SOD, higher amount of Hep-SOD radioactivity was found in the livers. Since livers are not the known target of ¹²⁵I, the most possible reason is that Hep-SOD binds to its specific targets in the livers.
School of Pharmaceuticlal Science, Shandong University, Jinan 250012, Shandong, China; College of Life Sciences, Qufu Normal University, Qufu 273165, Shandong, China.
J
J
Liu
T
T
Zhao
H
H
Tan
Y
Y
Cheng
J
J
Cao
F
F
Wang
D000818:Animals; D002942:Circular Dichroism; D006207:Half-Life; D006493:Heparin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008816:Mice, Jimpy; D017433:Protein Structure, Secondary; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D017382:Reactive Oxygen Species; D006493:Heparin; D013482:Superoxide Dismutase