Why do metabolites circulate?

Abstract

1. The aim of most metabolism and excretion processes is to remove the drug and drug related material from the body; however, in most cases metabolites are present in abundance in circulation.

2. To allow better in vitro/in vivo correlations a greater understanding of why metabolites formed in organs such as the liver are present in the circulation is necessary.

3. Separating metabolites into highly lipid permeable and low lipid permeable allows the role of passive efflux from the liver and active transport to be dissected.

4. Many drugs form glucuronide metabolites that circulate at high total concentrations and attention is drawn to low lipid permeability, efflux from the liver by MRP3, high plasma protein binding and restricted distribution as the explanation for this.

5. The use of metabolite maps is suggested as a way of displaying complex processes in a simple form.

Keywords::

• Circulating metabolites
• glucuronides
• transporters

Acknowledgements

The authors would like to acknowledge Drs. Barry Jones, Kath Fenner and Angus Nedderman for technical help, expert commentary and enthusiastic discussions.

Declaration of interest

The authors report no conflict of interest. The authors are responsible for the writing and content of the paper.