Pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male subjects

Abstract

Aims 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 μg kg⁻¹ for 1 or 3 h, or administered subcutaneously at 3–50 μg kg⁻¹ to volunteers. RhIL-11 was also administered at 3 μg 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 t_1/2 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 μg 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.

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