TABLE 1

Fitted consensus kinetic values for Caco-2 confluent cell monolayers

Substrate	Association with P-gp	Efflux Active P-gp		Dissociation from P-gp into Apical Membrane	Efflux from P-gp into Apical Chamber	Partition Coefficient into Inner Cytoplasmic Monolayer	Passive Permeability Coefficient at Steady State		Other Bidirectional Transporter
	k₁^{^a}	T(0)^{^a}	T(0) ^{^a}	k_r^{^b}	k₂^{^c}	K_PC^{^d}	P_BA^{^e}	P_AB^{^e}	k_B^{^f}	k_A^{^f}
	M⁻¹s⁻¹	P-gp/μm²	pmol/well	s⁻¹	s⁻¹		nm/s	nm/s	s⁻¹	s⁻¹
Amprenavir (n = 7)	(1.7 ± 0.5) × 10⁺⁸	176 ± 28	0.1 ± 0.02	(5.9 ± 1.6) × 10⁺⁴	10 ± 0.02	100 ± 2	437 ± 54	418 ± 53	0	0
Quinidine (n = 5)	Same as above	Same as above	Same as above	(1.1 ± 0.01) × 10⁺⁴	1.1 ± 0.01	350 ± 40	477 ± 103	373 ± 52	0	0
Loperamide (n = 7)	Same as above	Same as above	Same as above	(6.0 ± 0.02) × 10⁺⁴	0.26 ± 0.01	1500 ± 250	134 ± 50	195 ± 30	20 ± 0.3	0
Digoxin (n = 5)	Same as above	Same as above	Same as above	(2.0 ± 0.3) × 10⁺⁴	8.7 ± 0.32	100 ± 11	64 ± 10	66 ± 18	35 ± 0.7	0

↵^a k₁ And T(0) are fitted simultaneously using the data for all drugs, and are therefore noted by “same as above.” The unit P-gp/μm² can be converted to μmols P-gp per liter of inner apical membrane simply by dividing by 0.8 (Tran et al., 2005).
↵^b k_r Is the dissociation rate constant from the P-gp binding site into the apical bilayer.
↵^c k₂ Is the efflux rate constant from the P-gp binding site into the apical chamber.
↵^d The partition coefficient between the cytosol and the inner plasma/apical monolayer, K_PC. Cell membrane partition coefficients were estimated using data from 0.1 μm extruded unilamellar liposomes (Tran et al., 2005) whose lipid compositions roughly mimic the lipid compositions of the respective membrane monolayers: inner cytosolic, phosphatidylserine/phosphatidylethanolamine/phosphatidylcholine (1:1:1); apical outer phosphatidylcholine/sphingomyelin/cholesterol; and basolateral outer, phosphatidylcholine/cholesterol (2:1) (Lumen et al., 2013). Only the inner cytosolic monolayer partition coefficient, K_PC, is shown in this table.
↵^e P_BA and P_AB refer to the steady-state passive permeability coefficient in the presence of GF120918, B>A and A>B, respectively.
↵^f k_B And k_A refer to the first-order clearance rates (s⁻¹) for transport modeled as a bidirectional update transporter (Agnani et al., 2011).