Figure 4.

Steady state kinetic profiles for terbinafine N-dealkylation in Pathway 2. CYP2C19 (○) and 3A4 (□) metabolism of terbinafine yielded kinetics for desmethyl-terbinafine (A) for the Step 2.1 in Pathway 2 (Figure 1). This metabolite was then used as a substrate to measure the kinetics for naphthyl methylamine (B) and TBF-A (not shown, see Results) for Step 2.2a and 1-naphthaldehyde for Step 2.2b (C), as shown in Figure 1. The sets of data were fit best to the Michaelis−Menten equation (p < 0.05), and the corresponding constants are reported in Tables 1 and 2. A total of 12 experimental reactions were carried out with terbinafine or desmethyl-terbinafine as the substrate. Error bars denote standard deviations. Reaction conditions and data analyses were carried out as described in Experimental Procedures.