. Author manuscript; available in PMC: 2021 Sep 29.

Published in final edited form as: Pharm Res. 2020 Sep 29;37(10):208. doi: 10.1007/s11095-020-02927-4

Table II.

Clinically Insignificant Changes in Pharmacokinetic Parameters (Expressed as Ratios of Interaction / Control) in Drug-Drug Interaction (DDI) Studies with Apixaban as the Victim Drug

Victim Drug	Perpetrator Drug	Apixaban-Relevant Inhibitory Potential	Population	$\frac{M A T^{D D I}}{M A T^{C o n}}$	$\frac{t_{m a x}^{D D I}}{t_{m a x}^{C o n}}$	$\frac{A U C^{D D I}}{A U C^{C o n}}$	$\frac{C L / F^{D D I}}{C L / F^{C o n}}$	$\frac{V_{s s} / F^{D D I}}{V_{s s} / F^{C o n}}$	$\frac{M R T^{D D I}}{M R T^{C o n}}$	$\frac{t_{1 / 2, z}^{D D I}}{t_{1 / 2, z}^{C o n}}$	Percent ADC Extrapolation (DDI/Con)	Reference
Apixaban (10 mg PO; Single Dose)	Atenolol (100 mg PO; Single Dose)	Unknown / Not CYP3A4	Healthy Subjects (n = 15)^a	1.07^b	1.33	0.87	1.15^c	0.91^b	0.77^b	0.84	2%/3%	[22]
Apixaban (10 mg PO; Single Dose)	Cyclosporine (100 mg PO; 3 Days)	CYP3A4 (I/S) p-gp (I/S) BCRP (I)	Healthy Males (n = l2)^d	0.98^b	1.00	1.19	0.79	0.54^b	0.64^b	0.56	10%/10%	[23]
Apixaban (5 mg PO; Single Dose)	Enoxaparin (40 mg PO; Single Dose; Concurrent Dose)	Unknown	Healthy Subjects (n = 20)	1.01^e	1.00	1.07	0.93^c	–^e	–^e	0.98	3%/3%	[25]
Apixaban (5 mg PO; Single Dose	Enoxaparin (40 mg PO; Single Dose; 6 h after Apixaban)	Unknown	Healthy Subjects (n = 20)^f	0,95^e	1.00	1.12	0.89^c	–^e	–^e	1.12	3%/3%	[25]
Apixaban (10 mg PO; Single Dose)	Famotidine (40 mg PO; Single Dose)	Unknown / Not CYP3A4	Healthy Subjects (n = 18)	1.03^b	0.67	1.01	0.99^c	0.97^b	0.98^b	1.20	1%/2%	[26]
Apixaban (10 mg PO; Single Dose)	Tacrolimus (5 mg PO; 3 Days)	CYP3A4 (I) P-gp (I)	Healthy Males (n = 12)^d	0.99^b	1.00	0.77	1.26	0.83^b	0.66^b	0.58	9%/10%	[23]

Pharmacokinetic values reported in the table are based on published average values, unless otherwise noted

AUC, area under the curve; BCRP, Breast Cancer Resistance Protein; Con, control; CL/F, apparent clearance; CYP, cytochrome P450; DDI, drug-drug interaction; I, Intestine; MAT, mean absorption time; MRT, mean residence time; P-gp, P-glycoprotein; PO, oral administration; S, Systemic; t_max, time to maximal concentration; t_1/2,z, terminal half-life; V_ss/F, apparent volume of distribution at steady state

Interaction phase was n = 14

Ratios are calculated by digitization of published average plasma concentration-time profiles and performing non-compartmental and/or compartmental analysis

CL/F was calculated using known dose, reported AUC and Eq. 1

Subjects were the same for the cyclosporine and tacrolimus DDI studies

Pharmacokinetic curves were not published, thus neither V_ss nor MRT could be calculated. However, MAT was calculated by utilization of the single dose relationship between reported t_max and t_1/2,z, as previously described [20]

Interaction phase was n = 19