Pharmacokinetic and Pharmacodynamic Evaluation of Different PEGylated Human Interleukin-11 Preparations in Animal Models.

Autor:	Yu KM; Nansha Biologics (Hong Kong) Ltd, Unit 608-613, IC Development Centre, No. 6 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong. Electronic address: kyu@nansha-biologics.com., Yiu-Nam Lau J; Nansha Biologics (Hong Kong) Ltd, Unit 608-613, IC Development Centre, No. 6 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong., Fok M; Nansha Biologics (Hong Kong) Ltd, Unit 608-613, IC Development Centre, No. 6 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong; Faculty of Health Sciences, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau., Yeung YK; Nansha Biologics (Hong Kong) Ltd, Unit 608-613, IC Development Centre, No. 6 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong., Fok SP; Nansha Biologics (Hong Kong) Ltd, Unit 608-613, IC Development Centre, No. 6 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong., Hu TL; Biomedical Technology and Device Research Labs, Industrial Technology and Research Institute, 195, Sec. 4, Chung Hsing Rd., Chutung, Hsinchu, Taiwan 31040., Tsai YJ; Biomedical Technology and Device Research Labs, Industrial Technology and Research Institute, 195, Sec. 4, Chung Hsing Rd., Chutung, Hsinchu, Taiwan 31040., Choo QL; Nansha Biologics (Hong Kong) Ltd, Unit 608-613, IC Development Centre, No. 6 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2018 Nov; Vol. 107 (11), pp. 2755-2763. Date of Electronic Publication: 2018 Jul 10.
DOI:	10.1016/j.xphs.2018.06.024
Abstrakt:	Treating thrombocytopenia induced by chemotherapy remains an unmet-medical need. The use of recombinant human interleukin-11 (rhIL-11) requires repeated injections and induces significant fluid retention in some patients. Modification of human interleukin-11 with chemically inert polyethylene glycol polymer (PEG) may extend the peripheral circulation half-life leading to an improved pharmacokinetic and pharmadynamic profile. In this study, a number of rhIL-11 PEG conjugates were created to determine the optimal approach to prolong circulating half-life with the most robust pharmacological effect. The lead candidate was found to be a single 40-kDa Y-shaped PEG linked to the N-terminus, which produced a long-lasting circulating half-life, enhanced efficacy and alleviated side effect of dilutional anemia in healthy rat models. This candidate was also shown to be effective in myelosuppressive rats in preventing the occurrence of severe thrombocytopenia while ameliorating dilutional anemia, compared to rats receiving daily administration of unmodified rhIL-11 at the same dose. These data indicated that a single injection of the selected modified rhIL-11 for each cycle of chemotherapy regimen is potentially feasible. This approach may also be useful in treating patients of acute radiation syndrome when frequent administration is not feasible in a widespread event of a major radiation exposure. (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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