Table 3.

Percent distribution of ponatinib and its major metabolites in urine and feces after administration of a single oral 45-mg dose of [¹⁴C]ponatinib to humans

Matrix [collection interval]	Metabolite ID	Retention time (min)	% Distribution in matrix	% of total radioactive dose
Urinea [0–72 h]	M14	16.6–20.1	5.6	0.3
	M15	20.2–21.8	28.1	1.51
	M16	22.5–24.5	19.8	1.07
	M24	33.5–35.0	5.1	0.27
	M25–M41 clusterb	35.0–41.0	14	0.75
	Ponatinib	47.8–53.2	Trace levels	<0.05
Fecesa [0–144 h]	M23 clusterc	32.1–37.6	17.2	14.9
	M31	38.0–38.9	20.4	17.7
	M32–M35 clusterd	38.5–39.5	2.1	1.8
	M36/M38	39.2–40.5	3.2	2.8
	M39/M41	40.1–41.5	3	2.6
	M42/M43	44.8–49.8	9.6/3.4	8.3/2.9
	Ponatinib/M46, M47	47.8–54.0	23.7/3.2	20.5/2.8
	M49	55.4–57.5	3.1	2.7

TRA total radioactivity

^aOnly peaks containing >1.5% of the TRA were included

^bM25–M41 cluster: metabolites include M25, M29, M30, M31, M32, M33, M34, M35, M36, M38, M39, M41, and other co-eluting unknown metabolites individually accounting for approximately 0.1–3% of the urine radioactivity

^cM23 (N-despiperazinyl acid) cluster: Metabolites include M23, M24, M25, M26, M27, and other co-eluting unknown metabolites individually accounting for approximately 0.1–3% of the fecal radioactivity

^dM32–M35 cluster: Metabolites include M32, M33, M35, and other co-eluting unknown metabolites individually accounting for approximately 0.1–1.0% of the fecal radioactivity