Pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male subjects.
OBJECTIVE
To study the pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male volunteers following subcutaneous (s.c.) and intravenous (i.v.) administration.


METHODS
RhIL-11 was infused intravenously at 10-50 micrograms kg-1 for 1 or 3 h, or administered subcutaneously at 3-50 micrograms kg-1 to volunteers. RhIL-11 was also administered at 3 micrograms kg-1 s.c. once daily for 7 days. Plasma and urinary concentrations were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
RhIL-11 showed linear pharmacokinetics after both intravenous infusion and s.c. administration. Comparison of t1/2 and MRT values after i.v. administration with those after s.c. administration indicated that rhIL-11 pharmacokinetics after s.c. administration were absorption rate-limited. Bioavailability after s.c. administration was about 65%. Since RhIL-11 was not detected in urine after a single 50 micrograms kg-1 s.c. dose, rhIL-11 was considered to be eliminated by metabolism. There was no significant change in the pharmacokinetic profile of rhIL-11 following repeated s.c. administration.


CONCLUSIONS
RhIL-11 demonstrated linear pharmacokinetics at these dose ranges after single and repeated s.c. administration or constant-rate i.v. infusion in healthy volunteers.
Aoyama
K
K
Drug Metabolism Department, Yamanouchi Pharmaceutical Co., Ltd, Tokyo, Japan.
Uchida
T
T
Takanuki
F
F
Usui
T
T
Watanabe
T
T
Higuchi
S
S
Toyoki
T
T
Mizoguchi
H
H
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D017370:Interleukin-11 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D011786:Quality Control; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D012015:Reference Standards; D012044:Regression Analysis
D017370:Interleukin-11; D011994:Recombinant Proteins