Erratum: Development, Verification, and Prediction of Osimertinib Drug–Drug Interactions Using PBPK Modeling Approach to Inform Drug Label

Venkatesh Pilla Reddy, Michael Walker, Pradeep Sharma, Peter Ballard and Karthick Vishwanathan

CPT Pharmacometrics Syst. Pharmacol. (2018) 7, 321–330. https://doi.org/10.1002/psp4.12289; published online March 15, 2018.

There is an error in Table  1. In Column 2, in the 10th row under the “Interaction” section, the text should read “OATP1B3 inhibition” instead of “OATP1B1 inhibition”.

Table 1.

Osimertinib PBPK model input parameters

p	Parameters and models	Osimertinib	Source
Physiochemical properties	Molecular weight	499.61	Experimental data
	Log P	5.45	Experimental data
	pKa	Diprotic base	Experimental data
		pKa 1: 9.50
		pKa 2: 4.44
	B/P ratio	1	Experimental data
	fu, plasma	0.0133	Estimated value
	fu, gut	0.00132	Predicted by Simcyp
Dosage form	Film coated tablets, immediate release
Absorption	Absorption model	First order
	fa	0.82	User defined value, based on Dickinson et al.5
	ka (CV%)	0.24	Estimated value from Pop‐PK model Brown et al.7
	P eff,man	0.187 × 10−4 cm/s	Estimated based on clinical data
Distribution	Distribution model	Full PBPK
	Vss (L/kg)	6.497	Simcyp Predicted using method 2
Elimination	Clearance type	Enzyme kinetics
	CYP1A2 CLint (μL/min/pmol of isoform)	0.520	Retrograde approach
	CYP2A6 CLint (μL/min/pmol of isoform)	1.749
	CYP2C9 CLint (μL/min/pmol of isoform)	0.479
	CYP2E1 CLint (μL/min/pmol of isoform)	0.111
	CYP3A4 CLint (μL/min/pmol of isoform)	0.731
	CYP3A5 CLint (μL/min/pmol of isoform)	0.210
	Renal CL (L/h)	0.235
Interaction	CYP2C8 reversible inhibition Ki (μM)	11.4	Experimental data
	CYP3A4/5 reversible inhibition Ki (μM)	2.55	Experimental data
	CYP3A4 time‐dependent inhibition Ki (μM)	1090	Experimental data
	CYP3A4 time‐dependent inhibition Kinact (hr−1)	3.70	Experimental data
	CYP3A4/5 induction IC50 (μM)	0.117	Experimental data
	CYP3A4/5 induction Emax (fold)	10.78	Experimental data
	Fumic	0.0261	Experimental data
	Fuinc	1	Optimized value based on sensitivity analysis
	OATP1B1 inhibition Ki (μM)	22	Experimental data
	OATP1B3 inhibition Ki (μM)	52.5	Experimental data
	BCRP inhibition Ki (μM)	2	Experimental data
Population	Oncology patients based Cheeti et al.6
Clinical data	D5160C00001 (NCT01802632): Tablet monotherapy data single and multiple dose data
	D5160C00012 (NCT02157883): DDI study with itraconazole
	D5160C00013 (NCT02197247): DDI study with rifampicin
	D5160C00014 (NCT02197234): DDI study with simvastatin
	D5160C00019 (NCT02317016): DDI study with rosuvastatin

BCRP, breast cancer resistance protein; CL, clearance; CL_int, intrinsic clearance; DDI, drug‐drug interaction; E_max, maximum effect; OATP, organic anion‐transporting polypeptide; PBPK, physiologically based pharmacokinetic; Pop‐PK, population pharmacokinetic; V_ss, volume of distribution at steady state.