1.Sensitivity in typeⅠ hypersensitivity compared between BN rats and Wistar rats
Zhonggang LI ; Huidi QIN ; Huaishan WANG ; Yanqiu SHI ; Zhaoping LIU
Chinese Journal of Pharmacology and Toxicology 2010;24(1):30-34
OBJECTIVE To compare sensitivity in typeⅠ hypersensitivity between BN and Wistar rats, and to establish a sensitive and reliable determination system for typeⅠ hypersensitivity. METHODS BN and Wistar rats were sc given ovalbumin (OVA) 10, 20 and 40 μg·kg~(-1) every other day for 5 times and normal control group with sc normal saline. The total immunoglobulin E (IgE) levels in serum were determined with ELISA and the specific IgE levels in serum were determined by passive cutaneous anaphylaxis on the 21st day from the 1st injection. The blood pressure, serum histamine and tryptase levels were determined after challenge on the 22nd day. RESULTSTotal IgE, specific IgE, histamine and tryptase levels in serum significantly increased and blood pressure decreased in OVA 10, 20 and 40 μg·kg~(-1) BN rat groups compared with normal control group, while in Wistar rats these symptoms only appeared in OVA 40 μg·kg~(-1) group. CONCLUSION BN rats are more sensitive than Wistar rats in typeⅠ hypersensitivity. The blood pressure, serum total IgE, specific IgE, histamine and tryptase levels can be used as the important indicators in typeⅠ hypersensitivity.
2.The role of ADME evaluation in translation research of innovative drug.
Yao LIU ; Lan HONG ; Lushan YU ; Huidi JIANG ; Jianzhong CHEN ; Qin MENG ; Shuqing CHEN ; Su ZENG
Acta Pharmaceutica Sinica 2011;46(1):19-29
New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.