TABLE 3

Comparison of the physicochemical properties, percentage human oral absorption, Caco-2 permeability, and predicted transcellular permeability of nontraining set compounds

Pathway of absorption was based on percentage of human oral absorption and mechanistic studies (see footnotes). For compounds transported via transcellular diffusion the Caco-2 permeability (log P_app) can be estimated by the TTP model prediction with a residual between 0.3 and −0.3. Residual error >0.3 indicates a paracellular or active influx component; residual error <−0.3 indicates an active efflux component.

Non-Training Set Compound	Molecular Mass	Distribution Coefficient (log D)	Absolute Bioavailability	Caco-2 Permeability (log P_app)	Model Prediction (log P_app^trans)	Residual Error
	Da		%
Transcellular
Salicylic acid	138	−1.44^{^a}	100^{^a,^b}	−4.92/−4.89^{^c/^d}	−4.73	−0.19
Acetylsalicylic acid	180	−2.57/−2.34^{^c/^d}	100^{^a}	−5.62^{^c}	−5.84	0.22
Caffeine	194	0.02^{^a}	100^{^a}	−4.51^{^a}	−4.34	−0.17
Naproxen	230	3.3^{^e}	100^{^b}	−4.05^{^f}	−4.30	0.25
Aminopyrine	231	0.63^{^a}	100^{^a}	−4.44^{^a}	−4.34	−0.10
Nevirapine	266	1.81^{^a}	>90^{^a}	−4.52^{^a}	−4.37	−0.15
Carbamazepine	236	2.45^{^b}	95^{^b}	−4.21^{^g}	−4.31	0.11
Griseofulvin	353	2.47^{^a}	95^{^b}	−4.44^{^a}	−4.54	0.11
Fluvastatin	411	1.09^{^e}	95^{^b}	−4.64^{^h}	−4.71	0.07
Paracellular
Mannitol	182	−3.10^{^c}	16^{^a}	−5.58^{^c}	−6.52	0.94
Active uptake
Glucose	180	−2.83^ⁱ	100^{^b}	−4.70^{^f}	−6.25	1.55
Gly-Pro	172	−3.32^{^e}	100^{^b}	−5.21^{^h}	−6.47	1.26
l-Dopa	197	−1.22/−1.38^{^g,^j}	100^{^b}	−6.00^{^k}	−5.05	−0.95
Active efflux
Cimetidine	252	−0.4^{^k}	60^{^b}	−6.48^{^k}	−4.63	−1.85
Rhodamine 123	380	0.53^{^l}	Poor^{^m}	−5.79^{^l}	−4.65	−1.14
Talinolol	363	1.1^ⁿ	55^{^o}	−6.69^{^j}	−4.58	−2.12

↵a Experimental data from Yazdanian et al. (1998).
↵b Experimental data from Avdeef and Tam (2010).
↵c Experimental data from Artursson and Karlsson (1991) and Camenisch et al. (1998).
↵d Experimental data from the current study.
↵e Experimental data from MarvinSketch (2010).
↵f Experimental data from Lennernas et al. (1996).
↵g Experimental data from Alsenz and Haenel (2003).
↵h Experimental data from Hilgendorf et al. (2000).
↵i Experimental data from Mazzobre et al. (2005).
↵j Experimental data from Hosoya et al. (2010).
↵k Experimental data from Garberg et al. (2005).
↵l Experimental data from Troutman and Thakker (2003).
↵m Experimental data from Shen et al. (2006).
↵n Experimental data from Shirasaka et al. (2009).
↵o Experimental data from Gramatté et al. (1996).