Table 1

Unbiased kinetic parameters of amitriptyline biotransformation by lymphoblast-expressed human CYP isoforms

Pathway	CYP	K_m^1-a	S₅₀^1-a	V_max^1-b	A	K_s^1-a	Cl_int^1-c
N-Demethylation	1A2^1-d	63.5 ± 18.9		1.79 ± 0.23			28.2
	2B6	56.7 ± 8.8		0.25 ± 0.01			4.4
	2C8	9.74 ± 3.4		0.7 ± 0.13		70 ± 24.4	71.9
	2C9^1-d	50.5 ± 10.2		3.97 ± 0.32			78.6
	2C19	8.52 ± 1.3		4.22 ± 0.2		639 ± 131	495.3
	2D6	7.12 ± 0.6		1.49 ± 0.03		1688 ± 329	209.3
	3A4		70.5 ± 3.7	3.09 ± 0.09	1.91 ± 0.2		21.9
E-10 hydroxylation	2B6	98 ± 13.5		0.13 ± 0.01			1.33
	2D6	4.75 ± 0.35		2.71 ± 0.06		373 ± 30	570.5
	3A4	69.3 ± 9.7		0.4 ± 0.02			5.77

N-Demethylation by CYPs 1A2, 2B6, and 2C9, and E-10 hydroxylation by CYPs 2B6, and 3A4 were described by a Michaelis-Menten model (parameters V_max and K_mdenoting the maximal rate at saturating substrate concentrations and the Michaelis constant, respectively). N-Demethylation by CYP3A4 was described by a Hill model (S₅₀ denoting the substrate concentration at which 50% of the maximal rateV_max is reached, and A denoting the Hill coefficient). CYPs 2C8, 2C19, and 2D6 were described by a Michaelis-Menten model with uncompetitive inhibition by substrate (parameter K_s denoting the inhibition constant for uncompetitive inhibition by substrate).

↵1-a Values in micromolar concentration.
↵1-b Values in picomoles per minute per picomole of CYP.
↵1-c Intrinsic clearance in nanoliters per minute per picomole of CYP.
↵1-d Velocities at amitriptyline concentrations greater than 167 μM excluded in estimation of kinetic parameters.