Why do metabolites circulate?

Xenobiotica. 2012 Jan;42(1):107-26. doi: 10.3109/00498254.2011.630110. Epub 2011 Nov 24.


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

Publication types

  • Review

MeSH terms

  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Fluconazole / metabolism
  • Fluconazole / pharmacokinetics
  • Fluconazole / pharmacology
  • Glucuronides / metabolism
  • Humans
  • Liver / metabolism
  • Metabolome
  • Pharmaceutical Preparations / blood
  • Pharmaceutical Preparations / metabolism*
  • Pyrazines / metabolism
  • Pyrazines / pharmacokinetics
  • Pyrazines / pharmacology
  • Sitagliptin Phosphate
  • Triazoles / metabolism
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology


  • Antifungal Agents
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucuronides
  • Pharmaceutical Preparations
  • Pyrazines
  • Triazoles
  • Fluconazole
  • Sitagliptin Phosphate