Table 6

Category I: unambiguous nonsubstrates (NNN)

Compound Name	P_app A → B	Mass Balance A → B	P_app B → A	Mass Balance B → A	BA/AB Ratio	Effluxed (Y/N)	ATPase Assay Ratio	ATPase Activator (Y/N)	Calcein-AM Assay	Calcein-AM Inhibitor (Y/N)
	nm/s		nm/s						% max
Amantadine	186 ± 3.09	84.5	157 ± 14.2	94.3	0.84	N^6-a	0.97	N	2.10	N
Chlorpheniramine	562 ± 35.1	96.1	642 ± 36.2	95.3	1.14	N	0.97	N	−3.50	N
Doxorubicin	14.5 ± 13.1	107	9.73 ± 6.11	103	0.67	N^6-a ^6-b	0.95	N	0.69	N
Itraconazole	571 ± 26.1	90.2	552 ± 34.6	91.6	0.97	N	1.20	N	−0.23	N
Lidocaine	842 ± 179	117	825 ± 272	105	0.99	N	1.01	N	1.70	N
Mannitol	11.3 ± 2.71	91.7	9.15 ± 2.97	99.5	0.82	N^6-a	1.25	N	−0.35	N
Methotrexate	10.5 ± 0.13	95.2	7.06 ± 2.36	106	0.67	N^6-b	0.91	N	4.25	N
Practolol	12.4 ± 1.17	120	16.4 ± 1.61	107	1.32	N^6-a	1.42	N	−1.66	N
Propranolol	496 ± 51.2	74.1	514 ± 43.0	81.7	1.04	N^6-a	1.33	N	6.22	N
Pyridostigmine	10.2 ± 3.17	95.3	12.6 ± 1.55	108	1.24	N^6-a	0.89	N	−2.47	N
Ranitidine	14.4 ± 0.53	85.6	19.5 ± 0.56	89.5	1.35	N^6-a	1.23	N	2.92	N
Sumatriptan	9.53 ± 2.17	104	13.0 ± 1.82	110	1.37	N^6-a	1.23	N	0.62	N
Triamterene	185 ± 3.70	76.7	184 ± 7.47	76.4	0.99	N^6-a	1.12	N	1.17	N
Yohimbine	429 ± 36.1	85.4	501 ± 13.2	86.7	1.17	N	1.05	N	4.23	N
Mean	240		247		1.04		1.11		1.12
Median	99.8		88.3		1.02		1.09		0.93
Minimum	9.53		7.06		0.67		0.89		−3.50
Maximum	842		825		1.37		1.42		6.22

n = 14 compounds. See Experimental Procedures for details of each assay and criteria to determine interaction with Pgp.

Y, yes; N, no.
↵6-a Run in the presence and absence of 2 μM GF120918 to confirm if compound transported by Pgp.
↵6-b Run twice with results and mass balances similar between experiments.