Spreadsheet: 0eb5de3e-05f6-4b7c-9fb4-20c14cc2435c
Sheet: Figure S1. P.O. δ-toc PK

Figure S1. Pharmacokinetic parameters of δ-tocopherol after p.o. administration in male C57BL/6 mice.
Group 2 - δ-tocopherol after a PO dose of 10 mg/kg |  |  |  |  |  | Group 3 - δ-tocopherol after a PO dose of 50 mg/kg |  |  |  |  |  | Group 4 - δ-tocopherol after a PO dose of 250 mg/kg
Dose | Dose | PK parameters | Plasma | Brain | Liver | Dose | Dose | PK parameters | Plasma | Brain | Liver | Dose | Dose | PK parameters | Plasma | Brain | Liver
(mg/kg) | route | (unit) |  |  |  | (mg/kg) | route | (unit) |  |  |  | (mg/kg) | route | (unit)
10 | PO | Tmax (hr) | 2 | NA | 2 | 50 | PO | Tmax (hr) | 4 | NA | 4 | 250 | PO | Tmax (hr) | 2 | NA | 4
 | N=3 | Cmax (ng/mL) | 376 | NA | 538 |  | N=3 | Cmax (ng/mL) | 2660 | NA | 5810 |  | N=3 | Cmax (ng/mL) | 6910 | NA | 10800
 |  | T1/2 (hr) | 2.85 | NA | 3.31 |  |  | T1/2 (hr) | 10.3 | NA | 15.3 |  |  | T1/2 (hr) | 12.6 | NA | 13.4
 |  | AUClast (hr*ng/mL) | 1710 | NA | 2520 |  |  | AUClast (hr*ng/mL) | 19600 | NA | 40500 |  |  | AUClast (hr*ng/mL) | 43300 | NA | 96000
 |  | AUCINF(hr*ng/mL) | 1850 | NA | 3280 |  |  | AUCINF(hr*ng/mL) | 21000 | NA | 43100 |  |  | AUCINF(hr*ng/mL) | 44900 | NA | 99300
 |  | AUCtissue/AUCplasma (%) | NA | NA | 177.2972972972973 |  |  | AUCtissue/AUCplasma (%) | NA | NA | 205.2380952380952 |  |  | AUCtissue/AUCplasma (%) | NA | NA | 221.1581291759465
Group 5-δ-tocopherol after a cassette PO dose of 10 mg/kg δ-tocopherol and 240 mg/kg sesamin |  |  |  |  |  | Group 6 - δ-tocopherol after a cassette PO dose of 50 mg/kg δ-tocopherol and 240 mg/kg sesamin |  |  |  |  |  | Group 7 - δ-tocopherol after a cassette PO dose of  250 mg/kg δ-tocopherol and 240 mg/kg sesamin
Dose | Dose | PK parameters | Plasma | Brain | Liver | Dose | Dose | PK parameters | Plasma | Brain | Liver | Dose | Dose | PK parameters | Plasma | Brain | Liver
(mg/kg) | route | (unit) |  |  |  | (mg/kg) | route | (unit) |  |  |  | (mg/kg) | route | (unit)
10/240 | PO | Tmax (hr) | 4 | NA | 4 | 50/240 | PO | Tmax (hr) | 4 | NA | 4 | 250/240 | PO | Tmax (hr) | 2 | NA | 4
 | N=3 | Cmax (ng/mL) | 883 | NA | 2820 |  | N=3 | Cmax (ng/mL) | 2140 | NA | 4580 |  | N=3 | Cmax (ng/mL) | 7150 | NA | 18400
 |  | T1/2 (hr) | 9.95 | NA | 10.3 |  |  | T1/2 (hr) | 14.9 | NA | 10 |  |  | T1/2 (hr) | 11.2 | NA | 15.7
 |  | AUClast (hr*ng/mL) | 5420 | NA | 16200 |  |  | AUClast (hr*ng/mL) | 22400 | NA | 42100 |  |  | AUClast (hr*ng/mL) | 59600 | NA | 173000
 |  | AUCINF(hr*ng/mL) | 6220 | NA | 18900 |  |  | AUCINF(hr*ng/mL) | 26800 | NA | 44700 |  |  | AUCINF(hr*ng/mL) | 64700 | NA | 188000
 |  | AUCtissue/AUCplasma (%) | NA | NA | 303.8585209003215 |  |  | AUCtissue/AUCplasma (%) | NA | NA | 166.7910447761194 |  |  | AUCtissue/AUCplasma (%) | NA | NA | 290.5718701700155
Notes:
1. The linearity range of sesamin standard curves was 10.0-10000 ng/mL in plasma and 40.0-40000 ng/mL in brain and liver samples.
The linearity range of δ-tocopherol standard curves was 20.0-10000 ng/mL in plasma and 80.0-80000 ng/mL in brain and liver samples.
2. The average base levels of δ-tocopherol and sesamin in plasma, brain and liver were obtained from 21 naive mice.
3. The base levels of δ-tocopherol and sesamin in blank plasma, brain and liver samples were all detectable, but beyond the linearity range of the standard curves. So the 0 (pre-dose) concentration in plasma, brain and liver samples was set to BQL based on the current LLOQ.
4. No clinical findings were observed during the entire in life study.
5. The p.o. dosing solutions for all 7 groups were prepared in 100% corn oil. The appearance of the dosing solutions for group 1-4 were clear and suspension for group 5-7.
6. Brain and liver samples was homogenized with 3 volumes of PBS (pH 7.4) before sample extraction. The final brain concentration was adjusted with a dilution of 4,  assuming 1 g wet brain equals to 1 mL.
7. NA = Not available.