Profiling Drug Membrane Transport via Immobilized Artificial Membrane Chromatography

Jin      Sun; Tian-Hong      Zhang; Zhong-Gui      He

Abstract

The preclinical and clinical development attrition rates of new drugs are high due to the unfavorable pharmacokinetic properties such as poor intestinal absorption and inadequate target tissue penetration, etc. Drug disposition performance in nature consists of in vivo sequential membrane transporting processes and is based on the entry into and exit of drugs from cell, even for metabolism process requiring drug to be delivered to the site of metabolic enzymes. Efficient and reliable high throughput screening that predicts these membrane permeability properties as early as possible, in drug discovery and development program is accordingly desirable. Immobilized artificial membrane (IAM) chromatography, one of the biopartitioning modeling systems, covalently bonds monolayer of phospholipid analogs onto the solid surface of silica particles and emulates the process of drug-biomembrane interactions in terms of rapid chromatographic method. It is a valuably predictive model of drug membrane permeability and biological activity. The implementation of IAM chromatography in early drug discovery and development would effectively lower the preclinical and clinical development attrition rates, and would be able to increase the fraction of more drug-like drug candidates. The interaction mechanism of drug-IAM and its profiling in membrane transport were described in this review.

Keywords: iam chromatography, membrane transport, membrane interactions, quantitative retention/structure-activity relationship, biopartitioning modeling system, relationship

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