Table 3.

Summary of plasma and urinary metabolites (Study SD‐809‐C‐12)

Metabolite	Percentage of total sample radioactivity (Mean ± SD)
	[14C]‐Deutetrabenazine (n = 6)	[14C]‐Tetrabenazine (n = 6)
Plasma metabolites
α‐HTBZ (M6)	13.0 ± 4.6	4.0 ± 1.4
β‐HTBZ (M5)	8.3 ± 4.2	1.8 ± 1.5
Mono‐hydroxy metabolite of tetrabenazine (M4)a	12.9 ± 3.2	15.6 ± 4.9
2‐methylpropanoic acid metabolite of β‐HTBZ (M1)b	9.2 ± 3.6	4.1 ± 2.0
Sulfate of O‐desmethyl α‐HTBZ (M3)	4.0 ± 1.5	16.4 ± 5.6
Sulfate of O‐desmethyl β‐HTBZ (M2)	2.5 ± 1.1	6.4 ± 2.9
Subtotal for metabolites M1–M6	49.8 ± 8.1	48.2 ± 5.1
Additional minor metabolites (total)c	31.9 ± 7.1	30.0 ± 8.7
Total for plasma metabolites	81.7 ± 3.0	78.2 ± 12.4
Urine metabolites (cohort pool)
2‐methylpropanoic acid metabolite of β‐HTBZ (M1)	13.9	2.7
Mono‐hydroxy β‐HTBZ (2 isomers)	9.3	1.2
Sulfate of O‐desmethyl β‐HTBZ	10.5	14.2
Co‐elution: Glucuronide of α‐HTBZ plus sulphate of O‐desmethyl HTBZd plus mono‐hydroxy α‐HTBZ	15.3	3.8
Sulphate of O‐desmethyl α‐HTBZ	16.7	27.7
Subtotal for major metabolites	65.7	49.6
Additional minor metabolites (total)e	27.2	30.6
Total for urine metabolites	92.9	80.2

HTBZ, dihydrotetrabenazine.

^aIn subsequent analyses, M4 was determined to be a minor metabolite constituting 5.1 and 5.9% of total drug‐related material in plasma for [14C]‐deutetrabenazine and [14C]‐tetrabenazine, respectively.

^bAlso referred to as carboxylic acid.

^cAdditional minor plasma metabolites included a sulfate of O‐desmethyl HTBZ, a glucuronide of HTBZ, monohydroxy HTBZ, 9‐O‐desmethyl β‐HTBZ and mono‐hydroxy O‐desmethyl tetrabenazine.

^dDue to the very low intensity of the protonated molecular ion, no product ion spectra were obtained for this compound.

^eAdditional minor urinary metabolites included mono‐hydroxy tetrabenazine, β‐HTBZ, α‐HTBZ, mono‐hydroxy β‐HTBZ, sulphate of O‐desmethyl HTBZ, glucuronide of α‐HTBZ and mono‐hydroxy α‐HTBZ.