Disposition kinetics of cobalt mesoporphyrin in mouse, rat, monkey and dog.
1. Radiometric and UV analyses indicated > 95% unchanged cobalt mesoporphyrin (CoMP) in plasma after i.v. or i.m. administration. Blood clearance of CoMP is < 2% of hepatic blood flow in mouse and rat, and < 0.5% of hepatic blood flow in monkey and dog. CoMP elimination t1/2 ranged from 3.1 to 9.9 days in animals after i.v. administration. 2. CoMP is highly (> 99.5%) bound to plasma proteins, but has low affinity for blood cells (Kp < 0.15). The volume of CoMP distribution (Vss < 0.91/kg) is reflective of a distribution to total body water following i.v. administration to mouse, rat, monkey and dog. 3. [14C]CoMP reached highest levels in rat tissue between 1 and 4 days following i.m. injection. Liver, kidney cortex, lymph node, adrenal and spleen demonstrated greatest uptake of radiolabel. Concentration in tissues was readily detectable at 60 days post-dose. 4. CoMP was slowly absorbed after i.m. administration showing dose-dependent pharmacokinetics. The major route of radiolabel elimination was faecal excretion (54% of dose) in rat after an i.m. dose of [14C]CoMP. Approximately 1% of the 14C dose was recovered in the urine over 7 days post-dose. 5. As a polar metalloporphyrin, CoMP has low clearance, restricted tissue distribution and long elimination t1/2 in the laboratory animals.
Feng
M R
MR
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co, Ann Arbor, MI 48105, USA.
Rossi
D T
DT
Strenkoski
C
C
Black
A
A
Dehart
P
P
Lovdahl
M
M
McNally
W
W
D000818:Animals; D001345:Autoradiography; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003035:Cobalt; D004285:Dogs; D005243:Feces; D007700:Kinetics; D008252:Macaca fascicularis; D008652:Mesoporphyrins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker
D001798:Blood Proteins; D008652:Mesoporphyrins; C084061:cobalt mesoporphyrin; D003035:Cobalt