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Salivary caffeine metabolic ratio in alcohol-dependent subjects

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objectives

To determine whether caffeine (CA) clearance and salivary paraxanthine (PX)/CA ratio were altered in alcohol-dependent subjects and also whether salivary PX/CA ratio was affected by arylamine-N-acetylation 2 (NAT-2) genotypes.

Methods

Of 30 male individuals recruited in assessing PX/CA ratio and CA clearance by ingestion of CA, 13 were healthy control, 10 were alcohol-dependent subjects with abnormal liver function tests and 7 were alcohol-dependent subjects with normal liver function. CA and PX levels were analysed by means of high-performance liquid chromatography. CA clearance was calculated from concentrations of CA in saliva at various time intervals. In another study, PX/CA ratios were assessed in 46 healthy male subjects. Their NAT2 status was genotyped using polymerase chain reaction with restriction fragment length polymorphism assay.

Results

Salivary CA clearance was well correlated with plasma and salivary PX/CA ratios in a wide range of the clearance. Correlation between salivary PX/CA ratio and CA clearance was considered high from the first hour after CA ingestion and continued so for at least 9 h (r=0.94–0.96, P<0.001). PX/CA ratio in saliva was also well correlated with plasma PX/CA ratio (r=0.98, P<0.001). Salivary CA clearance in the control group was significantly higher than that of patients with abnormal liver function tests, i.e. (mean±SEM; 95% confidence limits; l/h/kg) 0.094±0.013 (0.064–0.124) and 0.044±0.019 (0.002–0.091), respectively, and not different from that of patients with normal liver function tests [0.107±0.017 (0.066–0.149)]. Similarly, the same is true for PX/CA ratio. NAT2 genotype status did not apparently affect PX/CA ratio.

Conclusion

Saliva-based PX/CA ratio was a convenient and robust method for assessment of CYP1A2 activity and liver function and it was shown to be altered in alcohol-dependent patients with mild abnormal liver function test.

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Acknowledgements

This work was supported in part by the Faculty of Medicine Research Fund of Khon Kaen University and the National Research Council of Thailand. We thank Dr. Kanokwan Kittiwatanakul of Jitavej Khon Kaen Psychiatric Hospital for her advice and facilitation of the study. This study complies with the current Thai laws.

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Authors and Affiliations

  1. Department of Pharmacology and Faculty of Medicine, Khon Kaen University, 40002, Thailand

    Veerapol Kukongviriyapan, Laddawan Senggunprai, Auemduan Prawan & Danu Gaysornsiri

  2. Department of Physiology, Faculty of Medicine, Khon Kaen University, 40002, Thailand

    Upa Kukongviriyapan

  3. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Khon Kaen University, 40002, Thailand

    Jareerat Aiemsa-ard

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  1. Veerapol Kukongviriyapan
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  2. Laddawan Senggunprai
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Correspondence to Veerapol Kukongviriyapan.

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Kukongviriyapan, V., Senggunprai, L., Prawan, A. et al. Salivary caffeine metabolic ratio in alcohol-dependent subjects. Eur J Clin Pharmacol 60, 103–107 (2004). https://doi.org/10.1007/s00228-004-0734-3

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  • DOI: https://doi.org/10.1007/s00228-004-0734-3

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