Pharmacokinetics of [125I]-recombinant human interleukin-11: 1. Absorption, distribution and excretion after subcutaneous administration to male rats.
Absorption, distribution, metabolism and excretion of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in rats were investigated. After a single administration, the concentration of radioactivity in the tissues was 2-6-fold higher in the liver and kidneys, and slightly higher in the gastrointestinal tract as compared to the plasma concentration. However, since the concentration in the other tissues was lower than the plasma concentration, the transport of rhIL-11 into tissues appeared to be low. Tissue radioactivity rapidly 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 radioactivity being found in urine and 7.9% in feces. When [125I]-rhIL-11 was administered to bile-duct cannulated rats, 44.4% of the dosed radioactivity was excreted into bile up to 48 h after administration. Most radioactivity in bile and urine was found in the TCA supernatant and low molecular weight fraction by HPLC analysis, indicating that rhIL-11 was eliminated from the body by metabolism.
Uchida
T
T
Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan.
Aoyama
K
K
Mori
K
K
Usui
T
T
Watanabe
T
T
Takariki
Y
Y
Asahara
N
N
Hirose
M
M
Kimura
T
T
Tateishi
M
M
Higuchi
S
S
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D006801:Humans; D007279:Injections, Subcutaneous; D017370:Interleukin-11 / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007408:Intestinal Absorption; D007457:Iodine Radioisotopes / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution
D017370:Interleukin-11; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins