Table 2.

Physicochemical characteristics and nonspecific binding. The concentration range is that used in the dialysis experiments. Log D_7.4 was determined as described in the Methods section. The concentration of microsomal protein was 1 mg ml⁻¹.

Compound	log D7.4	pKa	% ionization (pH 7.4)	Reported mean Km (µm) [reference]	Concentration range (µm)	Observed fu(mic)
Acids
Caffeine	0.3	13.9	0.0	180a [14]	20,250	0.96,1.1
S-Naproxen	−0.7	4.2	100.0	143b [18]	20,500	0.99,1.0
Phenytoin	2.1	8.3	11.1	30 [20]	20,200	0.85,0.89
Tolbutamide	0.5	5.3	99.1	120 [19]	20,500	0.97,1.1
Bases
Amiodarone	> 7.0	6.6	12.5	310 [17]	100	< 0.01
Amitriptyline	1.6	9.4	99.0	67 [15]	20–1000	0.35–0.73
Nortriptyline	1.1	9.7	99.3	21 [16]	20–1000	0.35–0.70

^aHigh affinity component of caffeine N3-demethylation

^bO-Demethylation pathway.