ミガーラスタット塩酸塩 - database.japic.or.jp

1 1 2. 3. 1 150mg 123mg 2 A10014. GLA 5. GLA 24. 6. 16 1 123mg 2 7. 2 12 12 8. 9. 244 1 2 11.

2 10% 5% 10% 1% 5% 15. 75% 55% 4 16. 13 123mg 3 2020 9 1 873999 23000 AMX00463000 2018 5 4 2 1 123mg mg Cmaxa ng/mL tmaxb h AUC0-infa ng h/mL t1/2c h 123 13 2124 11519 a % b c 1 123mg 4 123mg 12 4 2 123mg 12 mg day Cmaxa ng/mL tmaxb h AUC0-ta ng h/mL 123 4 11691 8942 142029 10638 841524 8582 a % b 19 123mg 1 1 1 5 3 Cmax ng/mL AUC0-inf ng h/mL 90% CmaxAUC0-inf 19

3 1561 9805 -- 19 1408 8451 , , 1 19 1323 6132 , , 1 19 1278 5668 , , 1 19 945 5890 , , % 10 123mg 75% 6 13 123mg V/F 3 In vitro 14C 1 100 mol/L 111% 7 6 14C 123mg 24 77% O- M1 M2 M3 13% 5 2 6% 8 In vitro CYP1A2 CYP2A6 CYP2B6 CYP2C8 CYP2C9 CYP2C19 CYP2D6 CYP2E1 CYP3A4/5 CYP1A2 CYP2B6 CYP3A4 9-11 6 14C 123mg 240 12 O- M1 M2 M3 55% 5% 8 In vitro BCRP P-gp MATE1 MATE2-K OAT1 OAT3 OCT2 BCRP BSEP P-gp MATE1 MATE2-K OATP1B1 OATP1B3 OAT1 OAT3 OCT1 OCT2 SGLT1 IC50 SGLT2 12-18 CLcr 90mL/min 8

4 60 CLcr<90mL/min 8 30 CLcr<60mL/min 8 15 CLcr<30mL/min 8 123mg 19 4 Cmax ng/mL AUC0-inf ng h/mL 90% CmaxAUC0-inf 8 2100 12397 -- 8 2191 14536 , , 8 1868 22460 , , 8 2078 56154 , , % 12 123mg 20 5 -Gal A a 90% -Gal A b 90% CmaxAUC0-infCmaxAUC0-inf 4 , , , , 5 , , , , 3 a 90% -Gal A b 90% CmaxAUC0-infCmaxAUC0-inf 3 , , , , 12 , , , , a / b / 17.

5 III 18 72 57 25 32 eGFR 30mL/ 123mg 18 2 1 18 12 123mg GLA 52 34 5 18 1 18 1 eGFRCKD-EPI 34 18 18 34 17 , 34 , 18 mGFRiohexol 34 18 18 34 16 , 34 , 18 95% mL/ lyso-Gb3 2 lyso-Gb3 g/m2 33 16 18 32 13 , 31 , 13 lyso-Gb3 nmol/L , 32 , 17 18 , 31 , 15 , 31 , 15 95% lyso-Gb3 18 29% 10/34 44% 8/18 30 eGFRCKD-EPI mGFRiohexol mL/ 31 mL/ 30 g/m2 28 32% 10/31 21 eGFRCKD-EPI 15mL/ eGFRCKD-EPI 90mL/ 24 33% 24 300mg III IV III 6 16 74 67 24 43 eGFR 30mL/ 123mg 6 18 123mg GLA 50 22 28 GL-3 3 GL-3 6 6

6 12 0/6 12 - 20 20 20 17 17 - 25 26 25 22 22 0/6 12 - 6 - 18 24 eGFRCKD-EPI mL/ 41 g/m2 27 22 18. GLA -Gal A GL-3 GLA -Gal A 23 -Gal A -Gal A -Gal A GL-3 24 -Gal A -Gal A -Gal A GL-3 GL-3 25 19. Migalastat Hydrochloride JAN 2R,3S,4R,5S -2- Hydroxymethyl piperidine-3,4,5-triol monohydrochloride C6H13NO4 HCl 4 244 C21.

7 22. 7 1 PTP23. 1 AA26551 2018 3 23 2 AA94762 2018 3 23 3 MGM115806 2018 3 23 4 FAB-CL-204 2018 3 23 5 AT1001-016 2018 3 23 6 AT1001-018 2018 3 23 7 0332-145-02 2018 3 23 8 AT1001-014 2018 3 23 9 CYP XT115084 2018 3 23 10 CYP XBL07624 2018 3 23 11 CYP XBL15798 2018 3 23 12 Amicus-01-02 Dec2014 2018 3 23 13 Amicus-02-28 Apr2015 2018 3 23 14 Amicus-04-03 Nov2015 2018 3 23 15 2011N125700_00 2018 3 23 16 2011125739_00 2018 3 23 17 OPT-2015-091 2018 3 23 18 OPT-2015-090 2018 3 23 19 AT1001-015 2018 3 23 20

8 AT1001-013 2018 3 23 21 AT1001-012 2018 3 23 22 AT1001-011 2018 3 23 23 Fan JQ, et al. Nat Med. 1999 5 1 Benjamin ER, et al. Mol Ther. 2012 20 4 Khanna R, et al. Mol Ther. 2010 18 1 GLA 24. 100-0005 6 2 19 0120-907-477 9 00 17 00 GLA GLA GLA 26 GLA 26 GLA 0120-907-477 e-mail 100-0005 6 2 19 A-04