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2015 12 12 876149 IF 2008 () 50mg NPI 1 () 50mg() 200mgNPI 1 () 200mg() (JAN) Clarithromycin (JANINN) 2006 3 15 2006 7 7 2006 7 7 TEL. 03-5833-5011FAX. 03-5833-5100 : 9:00 17:00 http://www.npi-inc.co.jp/medical.html IF 2015 12 PMDA http://www.pmda.go.jp/safety/info-services/drugs/0001.html

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IF IF 2008 21 4 IF 2008 IF 3IF IF 2008 MR PDF IT MR IF IF IF MR IF IF IF 4 IF IF IF 2008 9

. 1. 1 2. 1. 1. 2 2. 2 3. 2 4. 2 5. 2 6. 3 7. CAS 3. 1. 4 2. 4 3. 4 4. 5. 1. 6 2. 6 3. 6 4. 7 5. 8 6. 8 7. 8 8. 10 9. 10 10. 10 11. 11 12. 11 13. 11 14. 11. 1. 12 2. 13 3. 15. 1. 16 2. 16. 1. 19 2. 21 3. 21 4. 21 5. 21 6. 22 7. 22. 1. 23 2. 23 3. 23 4. 23 5. 23 6. 23 7. 24 8. 27 9. 30 10. 31 11. 31 12. 31 13. 32 14. 32 15. 32 16. 32. 1. 33 2. 33. 1. 34 2. 34 3. 34 4. 34 5. 34 6. 34 7. 34 8. 34 9. 35 10. 35 11. 35 12. 35 13. 35 14. 35 15. 36 16. 36 17. 36. 1. 37 2. 37. 1. 38 2. 38. 39

1 1991 200mgNPI 50mg NPI 481 11 4 8 2006 3 2006 7 200mgNPI 2013 6 2 1) Mycobacterium avium complex 2)QT (Torsades de pointes ) (Toxic Epidermal NecrolysisTEN) (Stevens-Johnson)PIE () 1

1 (1) 50mg NPI 200mgNPI (2) Clarithromycin (3) +++ 2 (1) (JAN) (2) Clarithromycin (JANINN) (3) mycin (x) 3 4 C38H69NO13 747.95 5 (2R, 3S, 4S, 5R, 6R, 8R, 10R, 11R, 12S, 13R)-5-(3, 4, 6-Trideoxy-3-dimethylamino--D-xylohexopyranosyloxy)-3-(2, 6-dideoxy-3-C-methyl-3-O-methyl--L-ribo-hexopyranosyloxy)-11, 12-dihydroxy-6-methoxy-2, 4, 6, 8, 10, 12-hexamethyl-9-oxopentadecan-13-olideIUPAC 2

6 CAM 7CAS 81103-11-9 3

1 (1) (2) (95) (3) (4) 220227 (5) 1) pka8.48 (37) (6) 1) ph1.2 (37) ph5.5 3.73mg/mL (37) ph6.8 0.51mg/mL (37) 0.12mg/mL (37) (7) 20 D 8797 (0.25g25mL100mm) 2 1) (ph) 50%(10 5 ) 2524 10% 3 (1)() (2)() (3)() (4) 4

4 5

1 (1) 50mg NPI 200mgNPI 50mg NPI :6.2mm,:3.7mm,:84mg 200mgNPI :8.7mm,:5.4mm,:250mg (2) (3) 50mg NPI NPI MP 200mgNPI NPI 614 (4)pH ph 2 (1)() 50mgNPI1 () 50mg() 200mgNPI 1 () 200mg() (2) 50mgNPI 80 6000 200mgNPI 80 6000 (3) 3 6

4 2) (1) 50mg NPI 401 6 PTP 755% RH 200mgNPI 401 6 PTP 755% RH (401 7556 ) 3 (2) 50mg NPI 251 755% RH 3 ( 40%) 200mgNPI 251 755% RH 3 ( 40%) (3) 50mg NPI 1000Lux/hr 60 Luxhr (25 ) 7.4% 53.0 % 200mgNPI 1000Lux/hr 60 Luxhr (25 ) 33.0 % 7

(4) 50mg NPI 402 3 200mgNPI 402 3 5 6 7 (1) 3) 1) 50mg NPI 50mg NPI 50mg NPI 50rpmpH1.2pH5.0pH6.8100rpmpH6.8 ph1.2 5-O -desosaminyl-6-o - methylerythronolide ph1.2(50rpm)ph5.0(50rpm) 8

ph6.8(50rpm) (50rpm) ph6.8 (100rpm) 2) 200mgNPI 200mgNPI 200mgNPI 50rpmpH1.2pH3.0pH6.8100rpmpH6.8 ph1.2 5-O -desosaminyl-6-o - methylerythronolide ph1.2(50rpm) ph3.0(50rpm) 9

ph6.8(50rpm) (50rpm) ph6.8 (100rpm) (2) 50mg NPI 200mgNPI 2 () 50rpm ph6.0 50mg NPI 30 80% 200mgNPI 30 75% 8 9 () 10 10

11. (C38H69NO13) 12. 13. 14. 11

1 50mgNPI 1. 2. MAC MAC MAC 200mgNPI 1. 2. MAC 3. MALT 12

200mgNPI (1) MALT (2) (3) (4) 2 50mgNPI 1. 11 kg1015mg23 11 kg 15mg23 2. MAC 11 kg15mg2 200mgNPI 1. 1400mg2 2. 1800mg2 3. 1200mg1 750mg3127 400mg 12 13

50mgNPI (1) (2) 11400mg (3) 1400mg2 2523 23 (4) MAC 4) (5) MAC 200mgNPI (1) (2) MAC MAC 4) (3) MAC 1 MAC (4) 1400mg2 2523 23 (5) 14 (6) 130mg120mg110mg 120mg120mg1 14

3 (1)2009 4 (2) (3) (4) (5) 1) 2) 3) 4) (6) 1) 2) 15

1 2 (1) 70S50S (2) 5) 200mgNPI200mg() 1 1) 1282 12 L.pneumophilia 82 12 2) C.trachomatis MIC 22 11 3) M.pneumoniaeYamaguchi 0.52 12 16

2 1) No. 200mgNPI (200mg() Staphylococcus aureus Staphylococcus epidermidis Moraxella (Branhamella) catarrhalis Streptococcus pyogenes Streptococcus pneumoniae Haemophilus influenzae Neisseria gonorrhoeae Peptostreptococcus anaerobius FDA209PJC-1 0.12 0.12 IID866 0.12 0.12 ATCC25238 0.06 0.06 IID689 0.06 0.06 IID553 0.06 0.06 IID554 IID988 4 4 ATCC49226 1 1 ATCC27337 0.06 0.06 ATCC43504 0.06 0.06 Helicobacter pylori ATCC43629 0.12 0.12 ATCC43579 0.06 0.06 Campylobacter jejuni ATCC33560 2 2 Legionella pneumophilia ATCC33152 ATCC33215 0.015 0.015 Chlamydia trachomatis D/UW-3/Cx 0.03 0.03 Mycoplasma pneumoniae FH 0.002 0.002 17

2) 200mgNPI (200mg() Staphylococcus aureus Staphylococcus epidermidis Moraxella (Branhamella) catarrhalis Streptococcus pyogenes Streptococcus pneumoniae Haemophilus influenzae Neisseria gonorrhoeae Peptostreptococcus anaerobius 10 0.25128 0.25128 10 0.12128 0.12128 10 0.060.25 0.060.25 10 0.06128 0.06128 10 0.06128 0.06128 10 28 28 10 0.251 0.251 10 0.064 0.064 Helicobacter pylori 10 0.0632 0.0632 Campylobacter jejuni Legionella pneumophilia Chlamydia trachomatis Mycoplasma pneumoniae 10 0.52 0.52 10 0.0080.015 0.0080.015 1 0.03 0.03 10 0.002 0.002 (3) 18

1 (1) (2) 6) -(3) (3) 6) 50mgNPI 50mgNPI1 ( 50mg ()) (AUCCmax) 90 log(0.80)log(1.25) AUCCmax 19

200mgNPI 200mgNPI1( 200mg()) (AUCCmax)90 log(0.80)log(1.25) AUCCmax (4) (5) (6) 20

2 (1) (2) (3) (4) (5) (6) (7) 3 4. (1) (2) (3) 10. (4) (5) 5. (1) (2)CYP450-7. (3) (4) (5) 21

6 (1) (2) (3) 7 22

1 2 (1) (2) () -7. (3)-7. 3 4 5 (1) (2) -8. (3) -7. (4) QTTorsades de pointes-8. (5)-9. 6 200mgNPI 23

7. P450 (CYP) 3A4 CYP3A4 P-P- CYP3A4 CYP3A4 CYP3A4 (1) QTTorsades de CYP3A4 pointes 24

(2) P- ( ) CYP3A4 () ( ) 25

CYP3A4 CYP3A4 CYP3A4 5 ( ) CYP3A4 CYP3A4 P- P- HIV CYP3A4 P- P- CYP3A4 26

CYP3A4 CYP3A4 8 (1) CYP3A4 27

(2) 1)() 2)QTTorsades de pointes()qt Torsades de pointes QT -5. 3)()ASTGOTALTGPT -GTPLDHAl-P 4)() 5)Toxic Epidermal NecrolysisTEN Stevens-Johnson() 6) PIE()X PIE 7)() 8)()CKCPK 9)() 10)() 11)() 12) 7) () 28

(3) AST (GOT) ALT (GPT) -GTPLDHAl-P CK (CPK) (4) MAC -GTPAl-PAST (GOT) ALT (GPT) BUN 29

200mgNPI (5) AST(GOT)ALT(GPT)LDH-GTPAl-P QT 1) 2) (6) (7) (8) -2(1) -8(2) -8(3) -8(5) (3 ) 9 30

10 50mgNPI (1) ( ) SD (15150mgkg) CD-1 (151,000mgkg) (3570mgkg) 70mg kg 9 1 (2) () 2.5 200mgNPI (1) ( ) SD (15150mgkg) CD-1 (151,000mgkg) (3570mgkg) 70mg kg 9 1 (160mgkg) (50mgkg) (500mgkg) (50mgkg) (25mg kg) (400mgkg) 4 (2) () 2.5 11 () 12 31

13 14 (1) 1) 2) in vitro () (2) (3) PTP PTP PTP 15 200mgNPI (1) (2,000mgkg) (15mgkg) 4 (500mgkg) (100mgkg) (25mgkg) 4 (2) 13 C- 13 C- 4 16 32

1 (1). (2) (3) (4) 2 (1) (2) (3) (4) 33

1 50mg NPI 200mgNPI 2 3 3 4 (1) -14. (2) -14. 5 6 50mg NPI 100 10 10500 10 50 200mgNPI 100 10 10500 10 50 7 50mg NPI PTP 200mgNPI PTP 8 50 200 50mg 200mg 34

9 1991 3 29 () 10 2006 3 15 50mg NPI 21800AMY10076000 200mgNPI 21800AMY10077000 11 2006 7 7 12 2007 3 23 200mgNPI 2009 11 2 50mg NPI MAC 2009 11 2 200mgNPI 2010 11 10 200mgNPI MALT 2011 7 25 200mgNPI 2013 6 18 200mgNPI 13 14 35

15 16 17 50mgNPI 200mgNPI HOT9 117409001 6149003F1066 620003919 117416801 6149003F2070 620003929 36

1 1) ()(Orange Book No.13) 2) () 3) () 4) Griffith, D. E. et alam. J. Respir. Crit. Care Med., 175,367, 2007 5) 563, 399, 2006 6) 7) 2 16 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances,2013 37

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