. Author manuscript; available in PMC: 2020 Jun 17.

Published in final edited form as: Chem Res Toxicol. 2019 Apr 10;32(6):1151–1164. doi: 10.1021/acs.chemrestox.9b00006

Table 1.

Michaelis–Menten Kinetic Constants for Terbinafine N-Dealkylation Pathways by CYP2C19^a

Steady-state kinetic constants for individual metabolites^c
pathway	step	substrate	V_max ^b	K_m (μM)	V/K
pathway 1	1.1	terbinafine		N-methyl-1-naphthyl-methylamine
			1300 ± 83	120 ± 22	11
	1.2	N-methyl-1-naphthyl methylamine		1-napthaldehyde
			250 ± 17	300 ± 41	0.83
pathway 2	2.1	terbinafine		desmethyl-terbinafine
			4300 ± 190	37 ± 6.7	120
	2.2a	desmethyl-terbinafine		1-naphthyl-methylamine
			810 ± 92	220 ± 55	3.7
	2.2b	desmethyl-terbinafine		1-naphthaldehyde
			1300 ± 59	150 ± 58	8.7
pathway 3^d,e	3.1	terbinafine		1-naphthaldehyde
pathway 3^d,e			410 ± 14	3.0 ± 0.83	140

Data fit best to the Michaelis–Menten equation over the Hill equation (P < 0.05) shown in Figures 3, 4, and 5. Values shown with standard deviations.

Units are pmol/min/nmol of protein.

Quantitation of TBF-A catalytic efficiency was not possible due to variable V_max values, while K_m values were consistent.

Pathway Step 3.2 was not studied due to the absence of authentic standards and low efficiency of the previous step in a human liver microsomal enzymatic system that obviates the significance of this pathway for TBF-A.

Limit of quantitation was calculated as the standard deviation of response divided by the slope of the standard curve.