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

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 (Cl_fe) of chlorzoxazone was compared with one-time-point clearance estimation (Cl_est) 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 Cl_fe.Results The concordance between Cl_est and Cl_fe was highest at 6 h. The minimal mean prediction error (MPE) of Cl_est as a percentage of actual mean Cl_fe was –4.2% at 6 h. Furthermore, regarding Cl_fe, there was a negligible difference (P=0.56) of bias between Cl_est at 3 h (MPE=–8.9%) and 6 h (MPE=–4.2%). The best concordance between MR and Cl_fe was found at 3 h (r=0.74; P<0.001).Conclusion All three single-dose-sample estimates, Cl_est 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.