Fig. 1.

Relationship between CYP3A5 expression and IC₅₀ values of KTZ and ITZ for the CYP3A-catalyzed metabolism of MDZ and TST in HLM. Relationship between CYP3A5 expression and IC₅₀ values of KTZ (A) and ITZ (B) for MDZ and KTZ (C) and ITZ (D) for TST metabolism. CYP3A5 expression represents CYP3A5 protein expression (pmol/mg) as a percentage of a total CYP3A protein expression in HLM (CYP3A4 pmol/mg + CYP3A5 pmol/mg). Solid and dotted lines represent simulated data and their 2-fold error ranges, respectively (see Materials and Methods); ●, ▲, and ■ represent observed data using HLMs with CYP3A5*1/*1, CYP3A5*1/*3, and CYP3A5*3/*3 genotypes, respectively. Data are presented as the mean ± S.D. (n = 3 determinations).