選択的SGLT2阻害剤 ̶2型糖尿病治療剤̶

1 2016 6 5 . 2015 9 873969.. mg 5 mg . 22600 AMX00540000 22600 AMX00541000. 2014 5 2014 5 . 2014 5 2014 5 . 2014 3 . sglt2 . 2 .. 1 2 .. 1 2 1 . 2 . 2 .. 3 6 . 3 .. 6 .. mg 5 mg . 1 1 mg 1 1 .. mg 5 mg . 5 mg 1 1 .. 1 . 1 .. 1 .. 2 . 400.. 3 .. 4 . 2 .. 3 .. mg . 4 .. mm mm mg .. 144 .. 2 . 1 . 5 mg .. mm mm mg . 286 .. 81.. 2 3 . CYP3A4/5 4A11 4F2 4F3B UGT1A1 .. 3 .. 4 .. 3 .. 5 DPP-4 . - .. GLP-1 . 6 eGFR .. 7 .. - .. 8 .. - .. MAO .. 9 .. 1 .. 2 . 4 . 1262 236 . 35 30 . 3 2 26 . 1 . 1 . 10 .. 11 - .. 12 .. 13 GLP-1 2 .. 14 .. 3 .. 4 .. 2 1 . 1 3 1 1 1 . mg .. M2 .. CRP . 2 .. Cmax tmax t1/2 AUC0- .. ng/mL h h ng h/mL . mg 100 1000 163. n 9 M2 122 NAG .. 5 2 2 . 1 2 mg 5 mg 1. 1 7 . 2 7 AUC0-24h . M2 mg 5 mg . 6 Cmax tmax t1/2 AUC .. 1 ng/mL h h ng h/mL . mg 1 119 864 132. n 8 7 136 899 148. 150 mg/kg/ 1 1 5 mg 5 mg 1 243 1690 271. AUC 47 n 8 7 299 1880 318.. 1 AUC0- 7 AUC0-24h . 3 1 . 9 mg . 2 5 30 . Cmax AUC0-72h 90.

2 / , , . 7 / , , . / , , / . , , . 8 2 3 . 1,5-AG 50 5000 ng/mL . 1,5- 1,5-AG in vitro .. 3 4 9 . 9 . PTP PTP O- M2 . PTP M17 . M8 M2 . M12 M2 sglt2 . sglt2 . 10 sglt2 M2 50 . 4 20 100 mg/kg/ 104 IC50 nmol/L in vitro . 100 mg/kg/ CYP3A4/5 4A11 . 1 1 5 mg AUC 18 4F2 4F3B UGT1A1 in vitro . CYP2C19 IC50. mol/L CYP1A2 2A6 2B6 2C8 2C9 .. 2D6 2E1 3A4 IC50 8 15 22 . 100 mol/L in vitro CYP1A2 2B6 . CYP3A4 in vitro . 2 6 - . CYP3A4 / .. Cmax AUC0- . 90 90 . 4 1 ,10 1 mg 5 mg n 12 , , . 9 mg . 72 n 12 , , . P- P-gp 250 mg 5 mg n 12 , , .. BCRP OATP1B1 OATP1B3 n 12 , , . OAT1 OAT3 OCT2 mg 5 mg 1 3 . OATP1B3 7 . n 12 , , . IC50 mol/L P-gp BCRP . OATP1B1 OAT1 OAT3 OCT2 50 mg 5 mg n 12 , , .. IC50 100 mol/L in vitro n 12 , , . 5 11 n 12 , , . 2 2 . 5 mg . 30 mg n 12 , , . 5 mg Cmax 1 1 .. 7 . Cmax tmax t1/2 AUC0- 2 M-III n 12 , , . eGFR 1 ng/mL h h ng h/mL g .. 90 M-IV n 12 , , . 272 2010 508 n 11 . 60 89 n 12 , , . 244 2070 395 50 mg 5 mg n 17.

3 45 59 .. 252 2160 878 n 12 , , . n 10 . 30 44 40 mg n 12 , , . 211 2060 414 5 mg n 13 1 1 .. 4 . 15 29 n 12 , , . 195 2420 657 n 6 . 25 mg n 12 , , . 5 mg 1 mL/ m2 1 1 .. 2 24 4 . n 12 , , . AUC0-24h 6 12 .. 5 mg Cmax .. 23 1 . 23 . Cmax tmax t1/2 AUC0- 1 . Child-Pugh ng/mL h h ng h/mL 2 .. 228 1800 427 280 1 mg mg 5. n 6 . mg 10 mg 1 1 12 . Class A . 228 1720 523. n 8 . HbA1c NGSP . Class B . 170 1780 260 HbA1c NGSP 2 . n 5 . mg/dL mg/dL .. 7 13 ,14 , , , . 65 24 5 mg n 57 . Cmax AUC0- .. 256 ng/mL 2050 307 ng h/mL , , , , , , mg 20 40 8 5 . n 56 . mg Cmax AUC0- 205 ng/.. mL 1930 290 ng h/mL . , , , , , , 5 mg . n 54 .. p LSD . , 95 .. 24 . 2 3 28 . 2 eGFR 30 mL/ m2 59 mL/. 158 mg min/1 .73 m2 2 145 . 1 1 24 mg 1 1 24 . HbA1c HbA1c . NGSP HbA1 c NGSP .. HbA1 c NGSP 2 . mg/dL mg/dL .. n 50 , . mg . , , , n 95 , , . n 79 .. p , 95 . , , , , , , mg . n 79 . mg 5 mg 1 .. 1 28 52 95 . p , 95 HbA1c NGSP . HbA1c.

4 NGSP 95 , . 3 25 . 2 . 299 mg 5 mg . 1 1 52 1 29 ,30 . HbA1c NGSP .. HbA1c NGSP 52 - 2 sodium glucose cotransporter 2 ; sglt2 . HbA1c NGSP 95 . , 52 .. 4 /299 2 sglt2 31 ,32 . sglt2 sglt2 . 2 26 ,27 Ki nmol/L in vitro .. 150 117 95 3 2 ,30 ,33 ,34 . - 105 DPP-4 111 1 2 Zucker Fatty db/db . 59 8 . 2 24 2 GK . mg 5 mg 1 1 52 20 . HbA1c NGSP 24 . 52 2 2 mg 5 mg 1 1 7 . HbA1c NGSP 24 . 52 .. 4 2 ,30 ,34 ,35 . , . n 150 1 2 Zucker Fatty . 2. , . n 117 . db/db 4 1 1 . - . n 105 . , . 2 GK .. , 20 . n 95 . DPP-4 . , . n 111 2 2 mg 5 mg . , . 1 1 7 . n 59 . 4 . AUC . , 95 .. 13 /150 3 /117 . 2 /95 DPP-4 . 1 /111 .. 1 /59 - .. 35 db/db LSFU00032 .. Luseogli ozin Hydrate . JAN . luseogli ozin INN . 2S, 3R, 4R, 5S, 6R -2-{5- 4-Ethoxyphenyl methyl . -2-methoxy-4-methylphenyl -6- hydroxymethyl . thiane-3, 4, 5-triol hydrate . 105-6333 1 -23- 1. 09 . C23H30O6S xH2O.. N, N- .. mg PTP100 PTP140 PTP500 . 500 . 5 mg PTP100 PTP140.}

5 1 LSFU00001 . 2 2 LSFU00002 . 3 in vitro LSFU00003 . 4 LSFU00004 . 5 sglt2 LSFU00005 . 6 in vitro LSFU00006 . 7 CYP in vitro LSFU00007 . 8 CYP in vitro LSFU00008 . 9 2 . LSFU00009 . 10 in vitro LSFU00010 . 11 2 . LSFU00011 . 12 LSFU00012 . 13 LSFU00013 . 14 Sasaki T., et al. : Adv. Ther. 31, 345 2014 LSFF00004 . 15 LSFU00014 . 16 LSFU00015 . 17 LSFU00016 . 18 LSFU00017 . 19 LSFU00018 . 20 LSFU00019 . 21 LSFU00020 . 22 LSFU00021 . 23 Seino Y., et al. : Curr. Med. Res. Opin. 30, 1231 2014 LSFF00006 . 24 Seino Y., et al. : Curr. Med. Res. Opin. 30, 1245 2014 LSFF00007 . 25 LSFU00024 . 26 LSFU00025 . 27 LSFU00026 . 28 2 .. LSFU00027 . 29 Kanai Y., et al. : J. Clin. Invest. 93, 397 1994 LSFS00001 . 30 Yamamoto K., et al. : Br. J. Pharmacol. 164, 181 2011 LSFF00001 . 31 sglt2 Ki LSFU00028 . 32 SGLT1 LSFU00029 . 33 db/db LSFU00030 . 34 GK LSFU00031 .. KY7F1.