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1. Curr Drug Metab. 2012 Apr 30. [Epub ahead of print]

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

Perera V, Gross AS, McLachlan AJ.

Faculty of Pharmacy, University of Sydney NSW 2006, Australia.

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.

PMID: 22554278 [PubMed - as supplied by publisher]