TY - JOUR
T1 - Comparison of chlorzoxazone one-sample methods to estimate CYP2E1 activity in humans
AU - Kramer, Iza
AU - Dalhoff, Kim
AU - Clemmesen, Jens O
AU - Loft, Steffen
AU - Poulsen, Henrik E
N1 - Keywords: Administration, Oral; Adult; Area Under Curve; Chlorzoxazone; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2E1; Humans; Male; Metabolic Clearance Rate; Time Factors
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
U2 - 10.1007/s00228-003-0695-y
DO - 10.1007/s00228-003-0695-y
M3 - Journal article
C2 - 14610624
SN - 0031-6970
VL - 59
SP - 775
EP - 778
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
IS - 10
ER -