Table 1.

Published Sigmoid E_max Models Describing Drug Metabolizing Enzyme and Transporter Ontogenies in the Liver

Enzyme or Transporter	Source	Data Type	Birth		Adult		Age50 (y)	Exp or h	Age Cap (y)	Reference Number
			E0 (pmol/mg)	Fbirth	Max (pmol/mg)	Fadult or Fmax
ADH1A	in vitro	Protein-QP	ND		426		0.842	0.84		[137]
ADH1B	in vitro	Protein-QP	1822		5220		0.775	40.6		[137]
ADH1C	in vitro	Protein-QP	21		2598		1.03	2.1		[137]
ALDH1A1	in vitro	Protein-QP	209		394		0.900	244		[137]
CES1	in vitro	Protein-QPe		0.20		1	1.10	0.56		[128]
CYP1A2	in vitro	Protein-IR		0.01		1.0	5.2	0.5		[109]
	in vivo	Activity		0.16		1.5	0.20	2.0	10.0d	[109]
	in vitro	Hybridh		0.08		1.05	1.69	1.1		[108]
	in vivo	Activity		0		1.6	1.05g	5.7	3.76d,g	[107]
CYP2A6	in vitro	Protein-IR		0.01		1.0	0.02	1.8		[109]
	in vivo	Activity		0.15		1.1	0.04	0.8		[109]
CYP2B6	in vitro	Hybridh		0.1		1	1	1		[108]
	in vitro	Protein-IR		1.0		1.0	ND	ND		[109]
	in vivo f	Activity		1.0		1.0	ND	ND		[109]
CYP2C8	in vitro	Hybridh		0.3		1	0.02	1		[108]
	in vitro	Protein-IR/mRNA		0.03		1.0	0.02	1.3		[109]
	in vivo	Activity		0.15		2.7	0.15	4.0	0.5d	[109]
CYP2C9	in vitro	Hybridh		0.17		1	0.016	0.53		[108]
	in vitro	Protein-IR		0.01		1.0	0.02	1.2		[109]
	in vivo	Activity		0.01		2.2	0.01	1.2	0.3d	[109]
CYP2C19	in vitro	Hybridh		0.3		1	0.28	2.44		[108]
	in vitro	Protein-IR		0.11		1.1	0.21	1.5		[109]
	in vivo	Activity		0.16		2.3	0.30	2.0	0.8d	[109]
CYP2D6	in vitro	Hybridh		0.036		1.0	0.1	1		[108]
	in vitro	Activity		0.07		1.0	0.02	2.6		[109]
	in vivo f	Activity		1.00		1.0	ND	ND		[109]
CYP2E1	in vitro	Hybridh		0.086		1.074	0.226	0.496		[108]
	in vitro	Protein-IR		0.03		1.0	0.14	0.6		[109]
CYP3A	in vivo	Activity		0.05		1.7	0.10	1.3	2.5d	[109]
CYP3A4/5	in vitro	Hybridh		0		1.061	0.66	0.78		[108]
CYP3A4	in vitro	Protein-IR		0.10		1	6.30	0.7		[109]
	in vivo	Activity		0		1	2.07g	3.9		[107]
CYP3A5	in vitro	Protein-IR/QP		1.0		1.0	1.0	1.0		[109]
FMO3	in vitro	Protein-QP	1.75		31.22		0.80	0.49		[134]
SULT1A3	in vitro	Protein-QP		85.26		96.83	0.9094	166.5		[144]
SULT1B1	in vitro	Protein-QP		37.75		116.8	0.9092	166		[144]
UGT1A1	in vitro	Protein-QP		0.27		1	7.5	0.5		[99]
UGT1A4	in vitro	Activity		0.235		1.25	0.502	2.77		[106]a
	in vitro	Protein-QP		0.01		1	3.6	0.9		[99]
UGT1A6	in vitro	Protein-QP		0.03		1	10.3	0.6		[99]
UGT1A9	in vitro	Protein-QP		0		1	8.2	0.5		[99]
UGT1A9/2B7	in vitro	Activity		0		1.1	2.18	0.063		[106]a
UGT2B7	in vitro	Protein-QP		0.02		1	2.6	0.4		[99]
UGT2B17	in vitro	Activity		0.612		2.08	17.4	40.6		[106]a
	in vitro	Protein-QP	0.11		1.31		13.5	7.5		[139]
			Mb 0.10		Mb 1.75		Mb 13.6	Mb 14.9
			Fb 0.05		Fb 0.65		Fb 10.7	Fb 1.8
OCT1	in vitro	Protein-QP	0.58		3.98		0.47	0.92		[82]c
OATP1B3	in vitro	Protein-QP	0.50		1.14		0.58	4.87		[82]c
P-gp	in vitro	Protein-QP	0.15		0.41		2.94	0.78		[82]c

Significant figures provided as they are presented in respective source material. Protein-QP and -IR refer to protein expression as determined by quantitative proteomics and immunoreactive methods respectively.

^aDevelopmental trajectories for UGT 1A1, 1A3, 1A6, 1A9, 2B4, 2B7, 2B10 and 2B15 activities described in reference by one-phase decay equations

^bData also presented separately for males (M) and females (F)

^cExpression of BCRP, MRP2, BSEP, MATE1 not influenced by age

^dOntogeny equation applicable up to an age cap due to average adult clearance not representing maximum clearance.

^eRepresents collective expression of both microsomal and cytosolic protein

^fUpreti et al state “in vivo data used to verify, but not develop, in vivo ontogeny”

^gRefers to postmenstrual age

^hOntogeny models from this were collectively developed from both in vitro expression and activity data but specific use of expression and/or activity data unclear for specific isoforms