Table 2

Physicochemical and microsomal binding data on compounds studied using 1 mg/ml rat liver microsomes

Compound	Charge Type	logD_7,4	pK_a	logP	fu_inc	log((1 − fu)/fu)
2-Ethoxybenzemide	Neutral	1.34		1.34^2-a	0.98	−1.69
Albendazole	Neutral	3.29		3.29^2-a	0.56	−0.10
Alprazolam	Neutral	1.84		1.84^2-a	0.82	−0.66
Amiodarone	Base	>5	8.7^2-b	>6.35^2-a	0.002	2.70
Astemizole	Base	4.14	8.35^2-c	5.14^2-a	0.012	1.92
Betaxolol	Base	0.42	9.38^2-d	2.40^2-a	0.62	−0.21
Bumetanide	Acid	0.31	4.5^2-b	3.21^2-a	0.92	−1.06
Carbamazepine	Neutral	1.54		1.54^2-a	0.87	−0.83
Cerivastatin	Acid	1.44	4.3^2-e	4.54^2-a	0.65	−0.27
Cinoxacin	Acid	−2.11	4.7^2-d	0.59^2-a	0.92	−1.06
Clomipramine	Base	3.27	9.38^2-b	5.25^2-a	0.038	1.40
Clozapine	Base	2.9	8.0^2-b	3.60^2-a	0.26	0.45
Colchicine	Neutral	0.82		0.82^2-a	0.94	−1.19
Dichloralphenazone	Neutral	−0.32		−0.32^2-a	0.94	−1.19
Glipizide	Acid	0.13	5.9^2-b	1.64^2-a	0.96	−1.38
Glyburide	Acid	2.19	5.3^2-f	4.29^2-a	0.82	−0.66
Indapamide	Neutral	1.76		1.76^2-a	0.96	−1.38
Indomethacin	Acid	0.89	4.5^2-b	3.79^2-a	0.81	−0.63
Isradipine	Neutral	3.75		3.75^2-a	0.34	0.29
Ketoprofen	Acid	−0.09	4.6^2-b	2.71^2-a	0.92	−1.06
Losartan	Acid	0.83	4.1^2-c	4.13^2-a	0.90	−0.95
Mebendazole	Neutral	2.90		2.90^2-a	0.70	−0.37
Methocarbamol	Neutral	0.36		0.36^2-a	0.84	−0.72
Metyrapone	Neutral	1.37		1.37^2-a	>0.97	<−1.51
Oxaprozin	Acid	1.61	4.2^2-e	4.81^2-a	0.87	−0.83
Phensuximide	Neutral	0.68		0.68^2-a	0.75	−0.48
Pimozide	Base	4.60	8.6^2-f	5.83^2-a	0.007	2.15
Piroxicam	Acid	−0.31	6.3^2-d	0.82^2-a	0.92	−1.06
Promethazine	Base	2.67	9.1^2-b	4.38^2-a	0.11	0.91
Propefenone	Base	1.63	9.62^2-b	3.85^2-a	0.15	0.75
Sulfadoxine	Acid	−0.73	5.75^2-b	0.93^2-a	>0.97	<−1.51
Sulindac	Acid	−0.04	4.5^2-b	2.86^2-a	0.86	−0.79
Tamoxifen	Base	5.02	8.7^2-f	6.34^2-a	0.003	2.52
Thioridazine	Base	3.59	9.5^2-b	5.69^2-a	0.009	2.04
Tolmetin	Acid	−1.02	3.5^2-b	2.88^2-a	0.94	−1.19
Trimeprazine	Base	2.60	9.2^2-e	4.41^2-a	0.081	1.05
Trioxasalen	Neutral	3.47		3.47^2-a	0.38	0.21
Verapamil	Base	2.57	8.92^2-f	4.10^2-a	0.37	0.23
Propranolol^2-g	Base	1.05	9.45^2-f	3.10^2-a	0.44	0.10
Imipramine^2-g	Base	2.38	9.50^2-b	4.48^2-a	0.16	0.72
Warfarin^2-g	Acid	0.75	5.00^2-b	3.15^2-b	0.94	−1.19
Chlorpromazine^2-h	Base	3.27	9.30^2-b	5.18^2-a	0.11	0.91
Diphenhydramine^2-h	Base	1.52	8.98^2-b	3.11^2-a	0.71^2-i	−0.39
Diltiazerm^2-h	Base	1.81	7.70	2.29^2-a	0.86^2-i	−0.80
Desipramine^2-h	Base	1.04	10.44^2-b	4.08^2-a	0.12^2-i	0.88
Amitriptyline^2-h	Base			4.96^2-b	0.081^2-i	1.05
Quinidine^2-h	Base	2.12	8.60^2-d	3.35^2-a	0.70^2-i	−0.37
Prednisone^2-h	Neutral	1.22		1.22^2-a	0.56^2-i	−0.10
Diazepam^2-h	Neutral	2.25		2.25^2-a	0.66^2-i	−0.29
Methoxsalen^2-h	Neutral	1.97		1.97^2-a	0.89^2-i	−0.89
Triazolam^2-h	Neutral	2.22		2.22^2-a	0.78	−0.55
Diclofenac^2-h	Acid	1.09	4.00^2-c	4.49^2-a	>0.97^2-i	<−1.51
Ibuprofen^2-h	Acid	0.98	4.40^2-f	3.98^2-a	0.91^2-i	−1.02
Tolbutamide^2-h	Acid	1.00	5.27^2-b	3.13^2-a	>0.97^2-i	<−1.51
Amobarbital^2-h	Neutral	2.07^2-b	7.96^2-b	2.07^2-b	>0.97^2-i	<−1.51
Hexobarbital^2-h	Neutral	1.49^2-b	8.37^2-b	1.49^2-b	0.96^2-i	−1.33

↵2-a Calculated using logP = logD_7.4 + log(1 + 10^7.4A+BpKa), where A = 1 and B = −1 for an acidic compound, and A = −1 and B = 1 for a basic compound (Taylor, 1990). LogP = logD_7.4 for compounds designated as being neutral.
↵2-b Data from Medchem Database (Daylight Chemical Information Systems, Inc., Mission Viejo, CA).
↵2-c Data from Therapeutic Drugs, 2nd ed., Churchill Livingstone, 1999.
↵2-d Data from Drug Data Handbook, 3rd ed., Adis Int. Ltd., 1998.
↵2-e Data calculated using ACDpK_a software, version 4.5 (Advanced Chemistry Development Inc. Toronto, ON Canada)
↵2-f Data from CMC-3D database (MDL Information Systems, Inc., San Leandro, CA).
↵2-g Data from rat liver microsomes, Obach (1997).
↵2-h Data from human liver microsomes, Obach (1999).
↵2-i Calculated from fu_inc measured at a concentration other than 1 mg/ml using eq. 9.