Measurement of CYP1A2 Activity: A Focus on Caffeine as a Probe

Author(s): Vidya Perera, Annette S. Gross, Andrew J. McLachlan

Journal Name: Current Drug Metabolism

Volume 13 , Issue 5 , 2012

Become EABM
Become Reviewer
Call for Editor


The drug metabolising enzyme CYP1A2 contributes to the metabolism of a number of medicines including clozapine, olanzapine and theophylline. These medicines display a high degree of inter-individual variability in pharmacokinetics and response. Measuring CYP1A2 activity in vivo can be an important tool to identify the factors that influence variability in drug pharmacokinetics and inform dose selection.

Caffeine is the only currently accepted probe to conduct in vivo phenotyping of CYP1A2. Despite the number of proposed matrices (biological fluid containing the drug and/or metabolite/s of interest) and metrics (mathematical formula relating the drug and/or metabolite/s to enzyme activity) proposed to measure CYP1A2 activity using caffeine, many of these are compromised by factors related to the specific metabolic pathway studied or pharmacokinetic characteristics of caffeine and its metabolites. Furthermore, questions regarding the appropriate study design and methodology to conduct studies to evaluate CYP1A2 activity have often been overlooked. These issues include the potential influence of a methylxanthine abstinence period prior to caffeine CYP1A2 phenotyping and the impact of caffeine formulation on determining CYP1A2 activity. This review aims to discuss the various CYP1A2 matrices and metrics with a particular focus on unresolved methodological issues.

Keywords: CYP1A2, probe, drug metabolism, saliva, plasma, phenotyping, CYP1A2 Activity, Probe, Caffeine, drug metabolising enzyme, clozapine, olanzapine, theophylline, dose, CYP1A2 matrices

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2012
Published on: 08 May, 2012
Page: [667 - 678]
Pages: 12
DOI: 10.2174/1389200211209050667
Price: $65

Article Metrics

PDF: 92