Pharmacokinetics and tissue distribution of human urinary tumor necrosis factor binding protein in mice.
Iodinated natural human urinary tumor necrosis factor binding protein I (125I-uTBP) was iv injected into BALB/c mice, and its pharmacokinetics and tissue distribution were assessed during a short-term (0-1 hr) and for a long-term (0-24 hr) period. The blood 125I-uTBP concentration displayed a biphasic pattern that was adequately described by a biexponential function with estimated half-lives of 0.1 and 3.8 hr. The apparent volume of distribution (Vc) of the central compartment was 3 ml, which approximated the mouse blood volume. The clearance (CL) derived either from a model-dependent or a model-independent method of analysis was 2.5 and 2.9 ml/hr, respectively. One hr after the iv administration of 125I-uTBP, the radioactivity accumulated in the major organs and tissues. The highest concentrations in terms of pg per organ were seen in the skin and in the liver. When expressed as pg 125I-uTBP per mg organ, the distribution was the highest in the gallbladder, bladder, kidneys, and lungs. At 24 hr, the distribution of 125I-uTBP represented about 10% of the amount measured at 1 hr. The rank order of accumulation of the radiolabeled uTBP in the major organs, expressed as pg per organ at 24 hr was skin greater than liver greater than kidneys greater than lungs greater than gut greater than spleen greater than gallbladder.
Gascon
M P
MP
Product Development Department, Ares Serono, Geneva, Switzerland.
Porchet
H C
HC
Le Cotonnec
J Y
JY
Ythier
A
A
Wallach
D
D
Piguet
P F
PF
Grau
G E
GE
D000818:Animals; D002352:Carrier Proteins / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014018:Tissue Distribution; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002352:Carrier Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1