Abstract
Purpose. To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-lra) in rats with established type II collagen arthritis.
Methods. Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-lra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-lra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-lra in CSEP or HA.
Results. Incorporation into HA led to slower release of IL-lra into the bloodstream and maintained therapeutic blood levels of IL-lra for a longer time compared to the IL-lra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-lra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-lra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-lra in HA resulted in 62% inhibition. IL-lra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics.
Conclusions. Administration of IL-lra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.
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Bendele, A., McAbee, T., Woodward, M. et al. Effects of Interleukin-1 Receptor Antagonist in a Slow-Release Hylan Vehicle on Rat Type II Collagen Arthritis. Pharm Res 15, 1557–1561 (1998). https://doi.org/10.1023/A:1011903100188
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DOI: https://doi.org/10.1023/A:1011903100188