PHARMACOKINETICS OF [I-125] RECOMBINANT HUMAN INTERLEUKIN-11 - 1 - ABSORPTION, DISTRIBUTION AND EXCRETION AFTER SUBCUTANEOUS ADMINISTRATIONTO MALE RATS

Absorption, distribution, metabolism and excretion of [I-125]-rhTL-11 (recombinant human interleukin-11) after subcutaneous administration i n rats were investigated. After a single administration, the concentra tion of radioactivity in the tissues was 2-6-fold higher in the liver and kidneys, and slightly higher in the gastrointestinal tract as comp ared to the plasma concentration. However, since the concentration in the other tissues was lower than the plasma concentration, the transpo rt of rhIL-11 into tissues appeared to be low. Tissue radioactivity ra pidly diminished, thus accumulation of rhIL-11 in tissues was thought to be low. Excretion of radioactivity into urine and feces was almost complete 72 h after administration, with 88.5% of the dosed radioactiv ity being found in urine and 7.9% in feces. When [I-125]-rhIL-11 was a dministered to bile-duct cannulated rats, 44.4% of the dosed radioacti vity was excreted into bile up to 48 h after administration. Most radi oactivity in bile and urine was found in the TCA supernatant and low m olecular weight fraction by HPLC analysis, indicating that rhIL-11 was eliminated from the body by metabolism.