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Comparison of chlorzoxazone one-sample methods to estimate CYP2E1 activity in humans

Abstract

Objective

Comparison of a one-sample with a multi-sample method (the metabolic fractional clearance) to estimate CYP2E1 activity in humans.

Methods

Healthy, male Caucasians (n=19) were included. The multi-sample fractional clearance (Clfe) of chlorzoxazone was compared with one-time-point clearance estimation (Clest) at 3, 4, 5 and 6 h. Furthermore, the metabolite/drug ratios (MRs) estimated from one-time-point samples at 1, 2, 3, 4, 5 and 6 h were compared with Clfe.

Results

The concordance between Clest and Clfe was highest at 6 h. The minimal mean prediction error (MPE) of Clest as a percentage of actual mean Clfe was −4.2% at 6 h. Furthermore, regarding Clfe, there was a negligible difference (P=0.56) of bias between Clest at 3 h (MPE=−8.9%) and 6 h (MPE=−4.2%). The best concordance between MR and Clfe was found at 3 h (r=0.74; P<0.001).

Conclusion

All three single-dose-sample estimates, Clest at 3 h or 6 h, and MR at 3 h, can serve as reliable markers of CYP2E1 activity. The one-sample clearance method is an accurate, renal function-independent measure of the intrinsic activity; it is simple to use and easily applicable to humans.

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Acknowledgements

The authors thank Anna Hansen for analytical assistance and the Danish Medical Research Council for financial support. The experiments complied with Danish laws.

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Correspondence to Kim Dalhoff.

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Kramer, I., Dalhoff, K., Clemmesen, J.O. et al. Comparison of chlorzoxazone one-sample methods to estimate CYP2E1 activity in humans. Eur J Clin Pharmacol 59, 775–778 (2003). https://doi.org/10.1007/s00228-003-0695-y

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  • DOI: https://doi.org/10.1007/s00228-003-0695-y

Keywords

  • Chlorzoxazone
  • Single sample clearance
  • CYP2E1