Preclinical pharmacokinetic evaluation to facilitate repurposing of tyrosine kinase inhibitors nilotinib and imatinib as antiviral agents

Table 1 Summary of preclinical PK parameters of nilotinib after a single intravenous or oral dose in preclinical species. Data, mean ± SD

PK parameter	C57BL/6 mice	Prairie dogs		Cynomolgus monkeys
IV Dose (mg/kg)	10	10		10
No. of animals	3^a	5		3
T^1/2 (h)	1.81	6.51 ± 2.97		7.79 ± 0.71
MRT (h)	2.21	6.7 ± 2.9		8.9 ± 1.1
CL (ml/hr./kg)	131.14	190 ± 77		639 ± 141
V_ss (ml/kg)	289.77	1157 ± 326		5737 ± 1783
AUC_0-inf (ng.hr./ml)	76,252	57,551 ± 15,508		16,135 ± 3296
Oral Dose (mg/kg)	10^b	20^b	10^c	10^c
No. of animals	3^a	5	6	3
T_max (h)	0.50	7.2 ± 1.79	5.6 ± 2.19	1.67 ± 0.58
C_max (ng/ml)	17,979	1673 ± 315	951 ± 255	410 ± 46
Apparent T^1/2 (h)	2.94	7.57 ± 2.01	3.5 ± 0.6	5.16 ± 0.52
AUC_0-inf (ng.hr./ml)	38,366	27,991 ± 6842	9329 ± 3630	2103 ± 468
Bioavailability (%)	50	24	16	13

^aper time point; ^boral dose prepared in NMP/PEG 300; ^coral dose prepared in Avicel/HPMC

ISSN: 2050-6511