TABLE 3.

ADMET parameter prediction of azithromycin and its related impurities in this study.

Principal descriptor	Azithromycin	Impurity J	Impurity E	Impurity F	Impurity K	Impurity H	Impurity I	Impurity L	Impurity Q	Impurity R	Impurity S
TPSA (Å2)	180.09	152.39	202.88	197.16	189.32	243.33	188.88	193.92	178.22	178.22	209.44
Log P a	1.9007	0.9755	1.2978	1.4273	1.2387	2.6182	1.5585	1.9133	2.4053	2.4053	2.0467
Absorption
Water solubility (log mol/L)	−4.133	−3.918	−4.073	−4.069	−4.049	−3.246	−4.104	−4.331	−4.621	−4.588	−4.164
Caco2 permeability (log Papp in 10−6 cm/s) b	−0.211	−0.122	−0.228	0.154	−0.074	0.289	−0.227	0.29	−0.012	−0.055	−0.149
Distribution
VDss (human, log L/kg)	−0.214	−0.09	−0.293	−0.43	0.245	0.065	−0.243	−0.514	−0.25	−0.151	−0.238
BBB permeability (logBB)	−1.857	−1.263	−1.772	−1.959	−1.847	−2.409	−1.856	−2.018	−1.677	−1.681	−1.882
Metabolism
CYP2D6 substrate	No	No	No	No	No	No	No	No	No	No	No
CYP3A4 substrate	Yes	No	No	Yes	No	Yes	Yes	Yes	Yes	No	No
Excretion
Total clearance [log (ml/min/kg)] c	−0.424	−0.472	−0.349	−0.271	−0.53	−0.824	−0.292	−0.426	−0.219	−0.133	−0.661
Toxicity
Hepatotoxicity	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes

^aOctanol/water partition coefficient.

^bLogarithm of the apparent permeability coefficient.

^cDrug clearance is measured by the proportionality constant CLtot.