Hepatic intrinsic clearance ( CL _int) of drugs is often predicted based on in vitro data that are obtained from the Michaelis–Menten analysis. While most of the metabolic rate-substrate concentration kinetic curves fit to the Michaelis–Menten equation, cytochrome P450 (CYP) and uridine 5′-diphosphate (UDP)-glucuronosyltransferases exhibit sigmoidal kinetics for certain drugs. In our study, the kinetics of CYP3A4-catalyzed carbamazepine 10,11-epoxidation in human liver microsomes was sigmoidal and fitted to the Hill equation, revealing the S ₅₀ value of 358 µ M , n of 2.0, and the V _max value of 463 pmol/min/mg. While the intrinsic clearance calculated from Michaelis–Menten parameters ( CL _int) overestimated the observed in vivo intrinsic clearance ( CL _{int, in vivo} ), the maximum intrinsic clearance calculated based on the Hill equation ( CL _max) exhibited better predictions of CL _{int, in vivo} . Such better prediction using the CL _max was also observed for other four drugs, all of which also exhibited sigmoidal metabolic rate-concentration curves, according to the literature data. However, even if we assume such Hill equation, intrinsic clearances predicted at their therapeutic concentrations from in vitro data were still much lower than their CL _{int, in vivo} , suggesting the existence of unknown factors causing discrepancy between in vitro intrinsic clearance in human liver microsomes and in vivo data. Thus, even if we assume sigmoidal kinetics, that would not be enough for accurate prediction of CL _{int, in vivo} , and it would be preferable to use CL _max to quantitatively extrapolate the in vitro data to in vivo clearance.