Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

被引:11
|
作者
Chiang, Po-Chang [1 ]
Nagapudi, Karthik [1 ]
Fan, Peter W. [2 ]
Liu, Jia [1 ]
机构
[1] Genentech Inc, SMPS, Global Res & Dev, San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
关键词
subcutaneous injection; pharmacokinetics; modeling; drug delivery; subcutaneous; PK/PD; exposure; LYMPHATIC ABSORPTION; SOLUBILITY; RELEASE; PERMEABILITY; PROFILE; SYSTEM; VOLUME;
D O I
10.1016/j.xphs.2018.06.003
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
With the rising cost of drug research, "do more with less" has become a new emphasis in the pharmaceutical industry. Consequently, the early analysis of pharmacokinetic/pharmacodynamic, efficacy, and safety parameters for a new drug target is critical for ensuring informed decision-making as soon as possible during the drug discovery process. When absorption, distribution, metabolism, and excretion properties of compounds are suboptimal which is especially true during the early stages of drug discovery, obtaining the desired exposure can be challenging via the most common routes (oral, intravenous). Therefore, subcutaneous (SC) injection is often explored as an alternate route of delivery. Although SC injection is used widely in the industry, information about how to model and predict the absorption of drugs administered via SC injection is not readily available. In the current research, we analyzed the absorption behavior of 12 model compounds covering a wide range of physicochemical properties following SC injection. We introduced a compound-specific parameter, the absorption factor from single SC injections of suspension doses of each compound, to aid in modeling and predicting of drug absorption profiles. The pharmacokinetic models derived in this study are capable of describing and predicting the absorption properties of SC injection for individual compounds. (C) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:109 / 119
页数:11
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