Diurnal variation in CYP1A2 enzyme activity in South Asians and Europeans

Authors

  • Vidya Perera,

    1. Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia
    2. Centre for Research and Education on Ageing, Concord Hospital, Concord, NSW, Australia
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  • Annette S. Gross,

    1. Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia
    2. Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline R & D, Ermington, NSW, Australia
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  • Andrew J. McLachlan

    Corresponding author
    1. Centre for Research and Education on Ageing, Concord Hospital, Concord, NSW, Australia
    • Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia
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Correspondence

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

E-mail: andrew.mclachlan@sydney.edu.au

Abstract

Objectives

Response to some medications can depend on time of administration throughout the day. This study investigated diurnal variation in cytochrome P450 1A2 (CYP1A2) activity in people of South Asian and European ancestry.

Methods

CYP1A2 activity was determined using the 4-h paraxanthine/caffeine saliva concentration ratio following a 100-mg oral dose of caffeine in healthy individuals of South Asian (n = 11) and European (n = 12) ancestry. Caffeine was administered in the morning and evening on three separate days.

Key findings

A higher CYP1A2 activity (mean ± standard deviation) was found in the morning (0.52 ± 0.17) when compared with evening (0.47 ± 0.17) (n = 23, P < 0.05). When stratified by ethnicity, a difference in CYP1A2 activity was found in the morning (0.43 ± 0.13) and evening (0.35 ± 0.05) for South Asians (P < 0.05), but not in Europeans (0.61 ± 0.15 and 0.56 ± 0.17, respectively). The intra-individual variation in CYP1A2 activity (% coefficient of variation, CV) of CYP1A2 activity ranged from 2.9 to 40.0% in the morning and 1.3 to 38.8% in the evening. Inter-individual CV was 32.1 ± 5.0% and 30.9 ± 6.4% in South Asians and Europeans, respectively.

Conclusions

This study observed diurnal variation of CYP1A2 activity in South Asians, resulting in lower enzyme activity in the evening.

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