Pharmacokinetics of [125I]-recombinant human interleukin-11:

Abstract

Placental transfer and excretion into milk of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in female rats were investigated. After administration of [125I]-rhIL-11 to rats on the 14th day of gestation, radioactivity in the kidney was the highest among excised tissues, being 3 times higher than that in the plasma at 1.5 h. Radioactivity in other tissues, including the mammary gland, ovary, uterus, placenta and amniotic fluid, was lower than that in the plasma. Although radioactivity in fetuses was detected 6 h after administration, the level was only 2% of the plasma concentration in dams, and the radioactivity was not found in fetal-derived TCA precipitates. These results indicate that rhIL-11 does not readily pass through the placenta into the fetus. After subcutaneous administration of [125I]-rhIL-11 to lactating rats 14 days after delivery, radioactivity in milk was 1.1-1.6 times that in the plasma of dams. Radioactivity in clotted milk in the stomachs of suckling infants was almost equal to that in the dam's milk; however, only a small amount of radioactivity was detected in infant kidneys.

Pharmacokinetics of Recombinant Human Endostatin in Rats

“…TCA-precipitated radioactivity assay measures parent (unchanged drug) and possible metabolites of endostatin, but not free iodide. TCA-based radioactivity assay has been widely used in the pharmacokinetic study of protein and peptide drugs [73,[85][86][87][88][89][90][91][92][93][94][95][96][97][98]. The high specificity and sensitivity of TCA-based radioactivity assay make it an important approach for quantification of proteins/peptides.…”

“…It is well established that 125 I-labeled therapeutic proteins and peptides are stable, which have been widely used in the pharmacokinetic studies [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84]. For example, 125 I-labeled angiostatin, a promising antiangiogenic protein with similar bioactivity to that of endostatin, was proved to be stable and has been used in a tissue distribution and pharmacokinetic study in mice [84].…”