High-throughput approaches for evaluating absorption, distribution, metabolism and excretion properties of lead compounds

Curr Opin Chem Biol. 1998 Jun;2(3):411-6. doi: 10.1016/s1367-5931(98)80017-3.

Abstract

Combinatorial chemistry methods and high-throughput screening for leads in industrial drug discovery have generated a potential bottleneck in the optimisation processes that seek to align potency with good pharmacokinetics in order to produce good medicines. This has resulted in the need for higher throughput methods of screening for absorption, distribution, metabolism and excretion properties. Significant progress has been made in throughput of in vivo pharmacokinetic studies, with the introduction of cassette, or multiple-in-one, protocols. In this technique, typically up to ten compounds are administered in one dose and analysed concomitantly on the mass spectrometer. High-throughput methods in in vitro absorption, distribution, metabolism and excretion are less well-developed as yet, and current approaches comprise automation of well-established methods for absorption using cell lines and metabolism using liver microsomes.

MeSH terms

  • Animals
  • Cell Line
  • Drug Design*
  • Drug Evaluation, Preclinical / methods
  • Intestinal Absorption
  • Lead / pharmacokinetics*
  • Lead / toxicity
  • Microsomes, Liver / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / toxicity
  • Tissue Distribution

Substances

  • Organometallic Compounds
  • Lead