Table I.

Physicochemical Properties ^a

Compound	CNS	log BB	MW	log POCT	α	β	π	R	Vx	Q	pKa	pKa	Ref
Alfentanil		0.0	417	2.4	0.00	2.45	2.62	2.18	3.26	0	6.25		13
Amitriptyline	+	1.3	277	4.8	0.00	0.77	1.31	1.71	2.40	+	9.49		38
Amoxapine		0.6	314	1.4	0.16	1.43	1.68	2.25	2.25	+	8.54	3.48	b
Antipyrine	−	−0.10	188	0.7	0.00	1.28	1.75	1.42	1.48	0			−
Astemizole	−	1.1	459	5.8	0.13	1.64	2.70	3.10	3.56	+	8.60	5.84	46
Atomoxetine		0.7	255	3.7	0.13	0.90	1.36	1.37	2.19	+	9.67		b
Bremazocine		0.6	315	3.2	0.73	1.35	1.28	1.82	2.58	+	10.30	8.50	c
Bupropion		0.4	240	3.0	0.13	0.94	1.32	1.07	1.94	+	8.20		d
Buspirone	+	0.4	386	2.5	0.00	2.16	2.18	2.22	3.03	+	7.59		d
Caffeine	+	−0.06	194	0.1	0.00	1.27	1.90	1.48	1.36	0	−		−
Carbamazepine	+	0.00	236	2.1	0.39	0.92	2.06	2.12	1.81	0			−
Cetirizine	−	0.1	389	2.4	0.57	1.76	2.24	2.05	2.94	±	7.45	3.10	39
Chlorambucil	−	−1.70	304	3.4	0.57	0.80	1.60	1.22	2.26	−	4.60	4.28	b
Chlorpromazine	+	1.06	319	5.3	0.00	0.99	1.83	2.26	2.41	+	9.24		38
Cimetidine	−	−1.42	252	0.7	0.74	1.86	1.87	1.66	1.96	0	6.13		d
Citalopram		0.10	324	3.9	0.00	1.08	1.87	1.66	2.53	+	9.31		b
Clozapine	+	0.7	327	3.2	0.18	1.44	1.82	2.46	2.43	+	7.90	4.40	38
Codeine		0.55	299	1.1	0.23	1.58	1.92	2.16	2.21	+	8.22		38
Colchicine		−0.8	399	1.1	0.26	2.08	3.32	2.17	2.99	0			−
Corticosterone	−	−0.5	346	2.3	0.48	1.62	2.80	1.90	2.74	0			−
Cyclosporin A		−0.8	1203	3.5	1.25	7.61	10.16	4.23	10.02	0			−
Daunomycin		−0.8	528	1.1	0.93	3.06	3.53	3.59	3.67	+	12.00	9.70	39
Deltorphin II		−6.0	783	−0.9	3.30	5.53	8.18	4.06	6.03	±	10.10	4.27	11
Diazepam	+	0.52	285	2.9	0.00	1.04	1.72	2.11	2.07	0	3.40		38
Digoxin		−1.23	781	1.3	1.58	4.32	4.46	3.67	5.75	0			−
Diltiazem	−	0.3	415	3.2	0.00	2.12	2.55	2.42	3.14	+	8.02		38
Diphenhydramine	−/+	0.7	255	3.9	0.00	0.95	1.43	1.36	2.19	+	9.10		11
Dipyridamole		0.0	505	1.8	0.95	3.03	2.90	3.74	3.87	0	6.22		46
Domperidone	−	−0.8	426	4.1	0.72	1.83	3.13	3.11	3.06	+	9.38	7.48	b
Doxepin	+	1.0	279	4.2	0.00	0.98	1.46	1.75	2.32	+	9.45		11
Doxorubicin		−0.83	544	0.5	1.17	3.34	3.69	3.75	3.73	+	12	9.70	b
DPDPE		−3.4	646	−0.3	2.30	4.04	5.81	3.87	4.77	±	10.10	3.50	11
Ergotamine		−1.1	582	1.4	0.79	3.69	4.60	4.56	4.21	0	9.49	7.26	b
Ethosuximide		−0.3	141	0.7	0.34	0.93	0.94	0.74	1.12	0	9.18		b
Etoposide		−1.1	589	0.5	0.60	3.23	4.11	3.38	3.90	0	8.53		d
Fentanyl	+	0.6	336	4.2	0.00	1.33	2.18	1.86	2.84	+	8.24		d
Fexofenadine	−	0.5	502	4.6	1.20	2.12	2.48	2.72	4.09	±	7.84	4.20	39
Fluoxetine	+	0.50	309	4.6	0.13	0.78	1.19	1.01	2.24	+	9.79		b
Fluphenazine		1.51	438	4.4	0.23	1.80	2.00	2.40	3.09	+	7.76	4.55	b
Flurbiprofen		0.3	244	4.0	0.57	0.58	1.51	1.50	1.84	−	4.18		38
Fluvastatin Acid		0.1	411	4.0	1.20	1.46	2.48	2.75	3.13	−	4.30		g
Galanthamine		0.00	287	1.2	0.31	1.45	1.92	1.89	2.17	+	8.62		b
Glibenclamide		−0.9	494	4.4	0.85	2.01	3.84	2.64	3.56	−	5.75		46
Haloperidol	+	1.34	376	3.6	0.31	1.45	2.08	2.00	2.80	+	8.65		38
Hydrocortisone	−	−0.9	362	1.8	0.73	1.90	2.92	2.04	2.80	0			−
Hydroxyzine	+	0.39	375	3.3	0.23	1.80	2.01	2.12	2.92	0	7.52	2.66	38
Ibuprofen		−0.18	206	3.6	0.57	0.51	1.01	0.78	1.78	−	4.59		38
Imatinib		−0.1	494	3.6	0.54	2.63	3.64	3.83	3.85	+	7.60	4.70	c
Indinavir	−	−0.74	614	3.4	0.98	3.59	4.27	3.63	4.90	0	4.91		11
Indomethacin	−	−1.26	358	4.3	0.57	1.24	2.49	2.44	2.53	−	4.57		38
Lamotrigine		−0.08	256	2.1	0.45	0.93	2.13	2.40	1.65	0	5.38		b
L-DOPA	−	−1.7	197	−2.7	1.56	1.44	1.77	1.33	1.43	±	8.77	2.21	39
Lidocaine	−/+	0.1	234	2.3	0.26	1.17	1.50	1.10	2.06	+	7.95		38
Loperamide	−	0.7	477	5.6	0.31	1.88	2.90	2.76	3.77	+	8.70		47
Lovastatin Acid		0.7	423	3.9	1.20	1.62	1.84	1.39	3.45	−	4.30		g
Loxapine		0.8	328	2.1	0.00	1.49	1.67	2.30	2.39	0	7.78		b
Maprotiline	+	1.3	277	5.0	0.13	0.68	1.27	1.76	2.33	+	10.35		c
Melphalan		−0.5	305	−0.1	0.78	1.37	1.90	1.43	2.22	±	9.3	1.9	c
Meperidine		0.6	247	2.4	0.00	0.97	1.26	0.99	2.05	+	8.58		11
Mesoridazine		−0.36	387	4.6	0.00	1.69	2.97	2.87	2.96	+	7.79		d
Methadone		0.9	309	4.2	0.00	1.09	1.72	1.51	2.71	+	8.99		48
Methotrexate		−2.4	454	−0.1	1.85	2.84	4.23	3.51	3.22	±	5.55	5.03	d
Metoclopramide		−0.7	300	2.4	0.50	1.63	2.31	1.50	2.34	+	9.71		49
Mirtazapine		0.53	265	3.0	0.00	1.22	1.67	2.08	2.11	0	7.91	4.21	b
Morphine	+	−0.16	285	0.9	0.50	1.47	1.59	2.23	2.06	+	9.26	8.18	38
Naltrindole		0.6	415	2.3	0.81	1.70	2.35	3.52	2.98	+	10.00	8.30	11
Naproxen	−	0.1	230	3.3	0.57	0.75	1.49	1.54	1.78	−	3.84		38
Naringenin		−0.8	272	2.6	1.30	1.14	2.19	2.23	1.89	0	10.40	7.27	d
Oxycodone		−0.3	315	0.5	0.23	1.80	2.28	2.18	2.26	+	9.00		b
Paclitaxel		−0.6	854	3.3	0.90	4.13	5.22	4.05	6.20	0			−
Pergolide		1.2	314	4.7	0.31	1.01	1.48	2.22	2.54	+	9.45		b
Perphenazine	+	0.7	404	4.2	0.23	1.84	2.33	2.87	3.02	+	8.50	4.10	b
p-F-Phenylalanine		−0.8	183	−1.3	0.78	1.02	1.36	0.87	1.33	±	9.23	2.20	11
Phenelzine		−0.2	136	0.8	0.34	0.99	1.02	0.98	1.20	+	7.66		b
Phenytoin		−0.14	252	2.5	0.44	1.14	2.04	1.94	1.87	0	8.31		38
Prazosin		−0.9	383	1.4	0.23	2.17	3.59	2.94	2.74	0	6.79		d
Probenecid		−0.4	285	2.9	0.57	1.29	1.92	1.25	2.16	−	3.16		38
Progesterone	+	0.2	314	3.6	0.00	1.04	2.49	1.56	2.62	0			−
Propranolol	−	0.64	259	2.9	0.29	1.36	1.44	1.76	2.15	+	9.53		38
Pyrilamine	+	0.49	285	3.2	0.00	1.45	1.73	1.66	2.39	+	8.8	4.9	c
Quercetin		−1.7	302	1.8	1.88	1.63	2.64	2.68	1.96	0	9.40	6.90	d
Quetiapine		0.7	384	2.8	0.23	2.01	1.93	2.72	2.91	0	7.30	2.27	38
Quinidine		−0.46	324	2.9	0.23	1.81	1.71	2.40	2.55	+	8.55	4.09	e
Quinine		0.6	324	2.9	0.23	1.81	1.71	2.40	2.55	+	8.55	4.09	38
Risperidone	+	−0.02	410	2.8	0.00	1.70	2.23	2.59	3.04	+	7.81		d
Ritonavir		−0.7	693	4.3	0.88	3.11	5.05	3.69	5.27	0	2.42		d
S-145		−0.3	377	4.1	0.69	1.48	2.63	2.01	2.88	−	4.90		c
Salicylic Acid	−	−1.10	138	2.4	0.70	0.40	1.10	0.91	0.99	−	3.02		38
Saquinavir	−	−0.95	671	4.1	1.46	3.89	5.55	4.09	5.30	0	6.91		d
Sertraline		0.80	306	5.0	0.13	0.67	1.44	1.83	2.26	+	9.20		f
SNC121		0.8	452	4.7	0.00	2.11	2.47	2.12	3.84	+	8.11	4.11	d
Sumatriptan	+/−	−0.4	295	1.3	0.68	1.61	2.05	1.90	2.27	+	9.64	8.93	b
Terfenadine	−	1.3	472	5.6	0.63	1.80	2.04	2.55	4.01	+	9.86		38
Testosterone	+	0.0	288	3.0	0.31	1.01	2.27	1.55	2.38	0			−
Theobromine		−0.28	180	−0.4	0.24	1.22	1.89	1.46	1.22	0	9.90		50
Theophylline	−	−0.29	180	0.0	0.35	1.29	1.99	1.46	1.22	0	8.55		38
Thioridazine	+	0.24	371	6.1	0.00	1.13	1.93	2.70	2.90	+	8.82		11
Tolbutamide		−0.7	270	2.2	0.59	1.15	2.21	1.33	2.06	−	5.19		d
Trazodone	+	0.3	372	3.5	0.00	1.92	2.47	2.64	2.73	0	7.46		b
Trifluoperazine		1.44	408	5.0	0.00	1.42	1.79	2.17	2.89	+	8.22	5.03	b
U69593		0.6	357	3.8	0.00	1.49	2.07	1.73	2.92	+	9.30		11
Valproic Acid	+	−0.22	144	2.6	0.61	0.46	0.54	0.21	1.31	−	4.90		c
Venlafaxine		0.6	277	3.6	0.31	1.16	1.23	1.20	2.37	+	9.72		b
Verapamil	−	−0.70	455	4.2	0.00	1.89	3.00	1.76	3.79	+	9.07		38
Vinblastine		−0.07	811	4.1	0.54	4.01	3.72	4.46	6.07	0	6.94	3.03	b
Vincristine		−1.03	825	3.1	0.54	4.25	4.30	4.59	6.08	0	7.40	5.42	c
Warfarin	−	0.0	308	3.1	0.31	1.23	2.28	1.98	2.31	−	4.75		d
Zidovudine		−0.89	267	−0.1	0.47	1.70	1.77	1.62	1.82	0	9.61		d

^aCNS indicates drug activity in the brain (9, 89-91). Log BB=brain-to-plasma total concentration ratio (92-94); values in italics calculated from Abraham descriptors (92). Values of log P_OCT and the Abraham descriptors were calculated by ADME Boxes v4.9 (ACD/Labs). Q refers to the charge class, based on the dominant calculated concentration fraction of the drug in a particular charge state.

^bThis work—potentiometric analysis using the Gemini Profiler (pION).

^cCalculated using ADME Boxes.

^dThis work—refined from PAMPA P_e vs. pH data using pCEL-X (pION).

^eSet equal to that of quinine.

^fThis work—estimated from pK_a determined at 37°C.

^gThis work—estimated from pK_a determination of rosuvastatin acid.