TABLE 1

Single-dose pharmacokinetics of endoxifen and tamoxifen in rats

	Endoxifen							Tamoxifen
	I.V.	P.O.						P.O.
Dose (mg/kg)	2	20	40	80	140	200	80	80
Formulation	HCl salt	HCl salt	HCl salt	HCl salt	HCl salt	HCl salt	Free Base	Citrate
Metabolite								ENDX	4HT	NDMT	TAM
C_max (ng/mL)	441	357	845	1176	1569	1676	1453	18	73	127	638
T_max (h)		4	2	8	2	12	2	6	2	2	2
Hlaf-Life (h)	6.3	5.8	14.6	10.7	21.7	34.4	13.6	6	2	2	2
AUC_0-24h (ng/mL*h)	790	5040	8500	21400	21100	30000	23800	281	1107	2464	12027
AUC_0-∞ (ng/mL*h)	840	5590	13000	33100	39300	95400	36200	855	2155	51534	20459
V_β (L/kg)	21.7
CL_app (L/hr/kg)^a	2.39	3.58	3.08	2.40	3.56	2.10	2.21	N/A	N/A	N/A	N/A
Absolute or relative bioavailability (%)		67	77	99	67	114	108	2.3	9.2	20.5	N/A

CL_app, apparent clearance; T_max, time to reach maximum plasma concentration.
^aFor intravenous doses, CL_app is Cl_p; for p.o. doses, CL_app is Cl/F.
^bRelative bioavailability of TAM metabolites was calculated by dividing the AUC_0-24h of the metabolite by the AUC_0-24h of tamoxifen and multiplying by 100.