In silico molecular targets, docking, dynamics simulation and physiologically based pharmacokinetics modeling of oritavancin

Table 4 ADMET prediction results

Type	Properties	Values
Absorption	Water solubility (log mol/L)	−2.892
	Caco-2 permeability (log Papp in 10 cm/s)	−1.874
	Intestinal absorption (human) (% Absorbed)	0
	Skin Permeability (log Kp)	−2.735
	P-glycoprotein substrate	Yes
	P-glycoprotein I inhibitor	No
	P-glycoprotein II inhibitor	No
Distribution	VDss (human) (log L/kg)	−0.274
	Fraction unbound (human)	0.34
	BBB permeability (log BB)	−3.923
	CNS permeability (log PS)	−6.421
Metabolism	CYP2D6 substrate	No
	CYP3A4 substrate	Yes
	CYP1A2 inhibitor	No
	CYP2C19 inhibitor	No
	CYP2C9 inhibitor	No
	CYP2D6 inhibitor	No
	CYP3A4 inhibitor	No
Excretion	Total Clearance (log ml/min/kg)	−2.059
Excretion	Renal OCT2 substrate	No
Toxicity	AMES toxicity	No
	Max. tolerated dose (human) (log mg/kg/day)	0.438
	hERG I inhibitor	No
	hERG II inhibitor	No
	Oral Rat Acute Toxicity (LD50) (mol/kg)	2.482
	Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day)	11.816
	Hepatotoxicity	No
	Skin Sensitisation	No
	T. Pyriformis toxicity (log ug/L)	0.285
	Minnow toxicity (log mM)	12.298

Based on pkCSM ADMET predictive model [32], a compound is said to have high Caco-2 permeability at a value of >0.90; poor GIA at less than 30% absorption; low skin permeability (logKp > −2.5); VDss is low at < 0.71 L/kg (log VDss < −0.15) and high at > 2.81 L/kg (log VDss > 0.45); BBB permeant at a logBB > 0.33 and non-permeant at logBB < −1; CNS permeant at a logPS > −2 and non permenat at a logPS < −3; Tetrahymena pyriformis toxicity (pIGC50) at a value > − 0.5 log µg/L is considered toxic; minnow toxicity (LC50) at a value < 0.5 mM (logLC50 < −0.3) is regarded as high acute toxicity; maximum recommended tolerated doses (MRTD) of ≤ 0.477 log(mg/kg/day) is considered low, and high if >0.477 log(mg/kg/day)

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