Abstract
Objective
This study was conducted to examine differences in flurbiprofen metabolism among individuals with the CYP2C9*1/*1, *1/*2, and *1/*3 genotypes.
Methods
Fifteen individuals with the CYP2C9*1/*1 (n=5), *1/*2 (n=5), and *1/*3 (n=5) genotypes received a single 50-mg oral dose of flurbiprofen. Plasma and urine samples were collected over 24 h, and flurbiprofen and 4′-hydroxyflurbiprofen pharmacokinetic data were compared across genotypes.
Results
CYP2C9 genotype was a significant predictor of flurbiprofen metabolism and accounted for 59% of the variability in flurbiprofen AUC0−∞, and approximately 50% of the variability in flurbiprofen oral clearance, formation clearance to 4′-hydroxyflurbiprofen, and the 0 to 24-h urinary metabolic ratio of flurbiprofen to 4′-hydroxyflurbiprofen. Flurbiprofen AUC0−∞ was significantly higher and all measures of flurbiprofen clearance were significantly lower in the CYP2C9*1/*3 individuals than in those with *1/*1. Significant differences in these parameters were not detected between *1/*2 subjects and *1/*1 subjects.
Conclusions
CYP2C9 genotype is a significant predictor of flurbiprofen disposition in humans by altering CYP2C9-mediated metabolism and reducing systemic clearance. The effects are most pronounced in individuals carrying the *3 allele.
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Acknowledgements
We acknowledge Cheryl Galloway for laboratory assistance, and the nursing staff of the UNC General Clinical Research Center for their help in performing the study. This investigation was supported in part by grant RR00046 from the General Clinical Research Centers program of the Division of Research Resources, National Institutes of Health.
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Lee, C.R., Pieper, J.A., Frye, R.F. et al. Differences in flurbiprofen pharmacokinetics between CYP2C9*1/*1, *1/*2, and *1/*3 genotypes. Eur J Clin Pharmacol 58, 791–794 (2003). https://doi.org/10.1007/s00228-003-0574-6
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DOI: https://doi.org/10.1007/s00228-003-0574-6