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Transcript of Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic...
![Page 1: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/1.jpg)
Tegoprazan (K-CAB)
SKKUSOM 이준행
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P-CAB (Tegoprazan, K-CABTM)
• 국내 제30호 신약 (code명: RQ-4, CJ-12420)
• Potassium
Competitive
Acid
Blocker
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위산과 위산분비억제제
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
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위산분비 억제제 개발의 역사
• Cimetidine, Ranitidine, Famotidine, Nizatidine, Roxatidine H2RA
• Omeprazole, Lansoprazole, Pantoprazole 1st PPI
• Rabeprazole, Esomeprazole, Dexlansoprazole, Ilaprazole 2nd PPI
• Revaprazan, Vonoprazan, Tegoprazan (K-CAB) P-CAB
![Page 5: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/5.jpg)
새롭고 강력한 위산분비억제제에 대하여 어떤 점을 고려해야 할 것인가?
• 약효 측면에서 기존 약제와 무엇이 다른가?
얼마나 새롭고 얼마나 강력한가?
• 안전한가? 장기 사용은 가능한가? 고령, 신질환, 간
질환에서 용량 조절이 필요한가?
• 편리한가? 약물 복용 시점, On demand therapy, 야
간 증상, 유전자형에 따른 차이
• 또 다른 새로운 특장점은 무엇인가? MMC
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오늘의 topic
• 위산과 위산분비억제제
• PPI vs tegoprazan
• Safety issues
• GERD에서 tegoprazan의 역할
• 결론: 새롭고 강력한 위산분비억제제
tegoprazan의 다양한 잠재적 적응증
![Page 7: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/7.jpg)
PPI vs Tegoprazan
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
![Page 8: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/8.jpg)
PPIs P-CAB
• Conversion to a reactive form
• Irreversible binding to the
external surface of acid pump
• Need to stimulate proton pump
• Directly binds to K+ Binding domain
at resting and stimulated state
• Reversible binding
• No need to stimulate proton pump
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Prodrug Conversion 후 작용
Active form 처음부터 바로 작용
어떤 약의 onset이 빠를까요?
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Reversible, competitive란 in vitro의
현상일 뿐입니다. 중요한 것은 in vivo!
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분류 P-CABs PPIs
Drug Tegoprazan Revaprazan Vonoprazan Esomeprazole Dexlansoprazole Rabeprazole
Chemical Structure
Formula (MW)
C20H19F2N3O3 (387.38) C22H23FN4 (362.44) C17H16FN3O3SC4H4O4 (461.46) C17H19N3O3S (345.41) C16H14F3N3O2S (369.363) C18H21N3O3S (359.444)
Derivatives Benzimidazole
Carboxamide Pyrimidine Sulfonyl Pyrrole Sulfinyl Benzimidazole
Chemical Name
(S)-(-)-4-[5, 7-Difluoro-3, 4-
dihydro-2H-chromen-4-
yl)oxy]-N,N,2-trimethyl-1H-
benzimidazole-6-carboxamide
N-(4-fluorophenyl)-4,5-
dimethyl-6-[(1RS)-1-methyl-
3,4-dihydroisoquinolin-2(1H)-
yl]pyrimidin-2-amine
1-[5-(2-Fluorophenyl)-1-
[(pyridin-3-yl)sulfonyl]-1H-
pyrrol-3-yl]-N-
methylmethanamine
(S)-5-Methoxy-2-[(4-methoxy-
3,5-dimethylpyridin-2-
yl)methylsulfinyl]-3H-
benzimidazole
(R)-(+)2-([3-methyl-4-
(2,2,2-
trifluoroethoxy)pyridin-2-
yl]methylsulfinyl)-1H-
benzo[d]imidazole
(RS)-2-([4-(3-methoxypropoxy)-
3-methylpyridin-2-
yl]methylsulfinyl)-1H-
benzo[d]imidazole
pKa 5.2 6.68 9.37 4.06 3.83 4.53
Tmax* 1.25h (0.5-4.0h) 1.4~2.2h 1.5h (0.75~3 h) 1.6h 4~5h 3.5h
Half life* 3.7~7.1h 14.8~26h 6.1~7h 1~1.5h 1~2h 1~1.5h
Indications NDA (EE, NERD),
P3 (GU, HP) GU, DU EE, GU,DU, HP EE, NERD, GU,DU, HP EE, NERD
EE, NERD, GU, DU,
HP
* Phase 1 clinical study report/FDA Label (Healthy subjects, Multiple dosing) ** EE: Erosive Esophagitis, NERD: Non-Erosive Reflux Disease, GU: Gastric Ulcer, DU: Duodenal Ulcer, HP: eradication of Helicobacter pylori.
In vivo 반감기 : 4-6 시간 - PPI의 반감기가 보통 1-2 시간임에 비하여 tegoprazan의 반감기는 매우 길다.
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In vivo: 위 조직 농도가 오래 유지됨
At 0.5hr
At 8hr
Ref. Clinical study report of [CJ_APA_101] study , KDDW 2017, P-UG-077, 078
0
2,500
5,000
7,500
10,000
0 4 8 12 16 20 24
Radio
act
ivity
(ngeq/m
g)
Time (hr)
Radioactivity of 14C-tegoprazan in SD rats
Plasma Stomach
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More stable in canaliculi
Akazawa. Therap Adv Gastroenterol. 2016;9:845-52
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Fast, strong and long
Andersson. Pharmacol Ther. 2005;108:294-307
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Benefits of K-CAB compared to PPI
• More potent acid suppression
• More rapid acid inhibition
• Better NAB control
• Less dependent on CYP2C19
• No food effect
• Optimal for H. pylori eradication
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1. More potent acid suppression
Shin et al. KDDW 2017
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2. More rapid acid inhibition
Day 1. Fast onset (within 0.5~1h ) Day 7. Fast onset (within 0.5~1h )
TEGOPRAZAN 50 mg
Day 1 54.5%
Day 7 68.2%
Greater acid-inhibitory effect in H. pylori (-) (Mean % time of pH 4)
Faster onset of acid-inhibitory effect
TEGOPRAZAN 50 mg
Day 1 Within 1 hour
Day 7 Within 1 hour
(Time to pH 4)
Ref. Clinical study report of [CJ_APA_108] study
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3. NAB control
PPI
Time after dosing (hr) at Day 7
7
6
5
4
3
0 2 4 6 8 10 12 14 16 18 20 22
2
1
Intr
agas
tric
pH
PPI
Ref. Modified illustration from Am J Gastroenterol 1998; 93: 763
Nocturnal Acid Breakthrough (NAB): >1 hr with pH<4
Does not necessarily denote a temporal relationship with symptom
Can deteriorate symptom and progress of GERD
PPIs can’t control NAB properly due to MOA & properties
NAB control of Tegoprazan
Tegoprazan: NAB control (morning dose)
Nocturnal Acid Breakthrough (NAB) vs.
12:00~4:00 am
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4. Less dependent on CYP2C19
• PPIs are strong inhibitors of CYP2C19.
– Individual variation by CYP2C19 polymorphism.
– Drug-drug interaction especially for clopidogrel.
• Dominant pathway of tegoprazan is CYP3A4
(75%).
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Individual variation
Adachi. Aliment Pharmacol Ther 2000;14:1259
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Tegoprazan metabolic pathway - 75% by CYP3A4
2018-9-29. K-CAB conference (신재국)
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5. No food effect No food effect on systemic exposures (AUC)
No food effect on PD
5.41 5.71
74.4 85.7
71.1
1) Arithmetic Mean
Ref. Br. J. Clin. Pharmacol 64:3 386–390.
- 9.8%
- 39.8%
Tegoprazan 200 mg
Esomeprazole 40 mg*
Ref. Clinical study report of [CJ_APA_102] study
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6. > pH 6: Tegoprazan bid > PPI bid - Optimal for H. pylori eradication
0 4 8 12 16 20 24
0
2
4
6
8
10
Intragast
ric
pH
Time (hr)
Day 7 Mean % time of > pH 6
88.03 % 58.34 %
Tegoprazan 50 mg, BID
Pantoprazole 40 mg, BID
Clinical study report of [CJ_APA_107] study
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강력한 산분비 억제가 필요한 이유
• H. pylori is more likely in a non-replicative state when
gastric pH is low (pH 3–6).
By raising pH, bacteria enter the replicative state
and become susceptible to amoxicillin and
clarithromycin.
• Increase the chemical stability of amoxicillin and
clarithromycin in gastric juice, thus preventing the
antimicrobials, which are fragile at lower pH levels,
from degradation
Malfertheiner. Gut 2016, Murakami. Gut 2016
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두 개의 3상 연구가 진행되고 있습니다.
CJ_APA_306
CJ_APA_307
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[CJ_APA_306] [CJ_APA_307]
등록률 350명/350명 (100%) 138명/284명 (48.6%)
선정·제외 기준 H. pylori 양성인 자
상부위장관 내시경 검사 상 다음의 어느 하나에
해당하는 자
- 소화성 궤양(위궤양 또는 십이지장궤양)
- 반흔기 상태의 위궤양 또는 십이지장궤양
- 위궤양 또는 십이지장궤양 기왕력이
있었던 자
- 만성 위축성 위염(chronic atrophic gastritis)
H. pylori 양성인 자
상부위장관 내시경 검사 상 다음의 어느 하나에
해당하는 자
- 소화성 궤양(위궤양 또는 십이지장궤양)
- 저등급 위 MALT 림프종
- EMR/ESD 치료 후 완전 절제된 조기
위암환자로서 제균 치료가 필요한 경우
- 만성 위축성 위염(chronic atrophic gastritis)
H. pylori
진단방법
UBT(필수) & CLO, 조직검사, 혈청검사,
대변항원검사 중 택 1
UBT(+) & 추가검사(+) ⇒ 양성으로 판정
UBT(필수) & CLO, 조직검사 중 택 1
UBT(+) & 추가검사(+) ⇒ 양성으로 판정
임상시험용의약품
투여방법
1일 2회, 7일, 식후 1일 2회, 7일, 식전
항생제감수성검사 위 전정부에서 2개 위 전정부 및 체부 대만에서 각각 1개씩
PUD 치료 Active, Healed Stage
GU, DU: 라니티딘(H2-RA) 28일 처방
Active stage
GU: 판토프라졸(PPI) 28일 처방
DU: 판토프라졸(PPI) 14일 처방
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Safety issues
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
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강력한 위산 분비 억제의 영향을 주시해야
Tegoprazan ?
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현장에서 걱정하는 부분은?
2019-1-24. Tegoprazan launching symposium (Seoul)
![Page 31: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/31.jpg)
간독성 등으로 개발이 중단된 약제들 - Chemocal class effect of imidazopyridine
• 기존 개발 진행 중에 중단되었던 P-CAB중에 일
부 물질들이 공통적으로 가지고 있던 구조가
"imidazopyridine"으로서 imidazopyridine이 간
독성을 유발하는 chemical class effect를 갖고
있음
![Page 32: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/32.jpg)
분류 P-CABs PPIs
Drug Tegoprazan Revaprazan Vonoprazan Esomeprazole Dexlansoprazole Rabeprazole
Chemical Structure
Formula (MW)
C20H19F2N3O3 (387.38) C22H23FN4 (362.44) C17H16FN3O3SC4H4O4 (461.46) C17H19N3O3S (345.41) C16H14F3N3O2S (369.363) C18H21N3O3S (359.444)
Derivatives Benzimidazole
Carboxamide Pyrimidine Sulfonyl Pyrrole Sulfinyl Benzimidazole
Chemical Name
(S)-(-)-4-[5, 7-Difluoro-3, 4-
dihydro-2H-chromen-4-
yl)oxy]-N,N,2-trimethyl-1H-
benzimidazole-6-carboxamide
N-(4-fluorophenyl)-4,5-
dimethyl-6-[(1RS)-1-methyl-
3,4-dihydroisoquinolin-2(1H)-
yl]pyrimidin-2-amine
1-[5-(2-Fluorophenyl)-1-
[(pyridin-3-yl)sulfonyl]-1H-
pyrrol-3-yl]-N-
methylmethanamine
(S)-5-Methoxy-2-[(4-methoxy-
3,5-dimethylpyridin-2-
yl)methylsulfinyl]-3H-
benzimidazole
(R)-(+)2-([3-methyl-4-
(2,2,2-
trifluoroethoxy)pyridin-2-
yl]methylsulfinyl)-1H-
benzo[d]imidazole
(RS)-2-([4-(3-methoxypropoxy)-
3-methylpyridin-2-
yl]methylsulfinyl)-1H-
benzo[d]imidazole
pKa 5.2 6.68 9.37 4.06 3.83 4.53
Tmax* 1.25h (0.5-4.0h) 1.4~2.2h 1.5h (0.75~3 h) 1.6h 4~5h 3.5h
Half life* 3.7~7.1h 14.8~26h 6.1~7h 1~1.5h 1~2h 1~1.5h
Indications NDA (EE, NERD),
P3 (GU, HP) GU, DU EE, GU,DU, HP EE, NERD, GU,DU, HP EE, NERD
EE, NERD, GU, DU,
HP
* Phase 1 clinical study report/FDA Label (Healthy subjects, Multiple dosing) ** EE: Erosive Esophagitis, NERD: Non-Erosive Reflux Disease, GU: Gastric Ulcer, DU: Duodenal Ulcer, HP: eradication of Helicobacter pylori.
PPI는 모두 유사한 모양이지만 P-CAB은 서로 다른 구조식을 가지고 있음
![Page 33: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/33.jpg)
Tegoprazan safety profile
![Page 34: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/34.jpg)
현재까지의 임상 연구에서 유의한 heptotoxicity를 보이지 않음
![Page 35: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/35.jpg)
Vonoprazan은 hypergastrinemia가 문제
![Page 36: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/36.jpg)
Tegoprazan은 lansoprazole과 유사한 정도
![Page 37: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/37.jpg)
Esomeprazole과도 유사한 정도
![Page 38: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/38.jpg)
GERD에서 Tegoprazan의 역할
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
![Page 39: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/39.jpg)
현장에서 기대하는 부분은?
2019-1-24. Tegoprazan launching symposium (Seoul)
![Page 40: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/40.jpg)
현장에서 기대하는 부분은?
2019-1-24. Tegoprazan launching symposium (Seoul)
![Page 41: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/41.jpg)
1. Erosive esophagitis의 초치료
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
![Page 42: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/42.jpg)
Erosive esophagitis에서 PPI가 효과가 좋다는 것은 누구나 아는 일입니다.
Chiba N et al. Gastroenterology 1997;112:1798
2 4 6 8 12
0
20
40
60
80
100
Weeks
% T
ota
l h
ea
led
PPI 11.7%/wk
H2RA 5.9%/wk
Placebo 2.9%/wk
Endoscopic healing
Weeks
% T
ota
l h
ea
rtb
urn
fre
e
0
20
40
60
80
1-2 3-4 5-6
PPI 11.5%/wk
H2RA 6.4%/wk
Relief of symptoms
![Page 43: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/43.jpg)
Tegoprazan (K-CAB) for ERD
![Page 44: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/44.jpg)
Tegoprazan (K-CAB) for ERD
![Page 45: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/45.jpg)
Tegoprazan (K-CAB) for ERD
![Page 46: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/46.jpg)
Tegoprazan (K-CAB) for ERD
![Page 47: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/47.jpg)
아마도 위산 분비 억제능력이 더 좋기 때문일 것입니다.
Shin et al. KDDW 2017
![Page 48: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/48.jpg)
환자들이 PPI를 매우 좋아했습니다. 그런데 증상 호전에는 며칠이 필요했습니다.
![Page 49: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/49.jpg)
첫 dose부터 onset이 아주 빠른 tegoprazan이라면 어떤 효과를 보일까요?
Shin et al. KDDW 2017
![Page 50: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/50.jpg)
어쩌면 증상 개선은 훨씬 더 빠르고 장기적인 healing rate는 비슷하거나 조금 더 나은 정도일지 모릅니다.
Andersson. Pharmacol Ther. 2005;108:294-307
![Page 51: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/51.jpg)
GERD 초치료와 유지요법의 새로운 전략
Mori and Suzuki. J Neurogastroenterol Motil 2019;25:6-14
![Page 52: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/52.jpg)
2. Non-erosive reflux disease
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
![Page 53: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/53.jpg)
Tegoprazan (K-CAB) for NERD
![Page 54: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/54.jpg)
Tegoprazan (K-CAB) for GERD
![Page 55: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/55.jpg)
3. Refractory GERD
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
![Page 56: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/56.jpg)
Approaches to PPI-refractory GERD
pH-impedance (= physiologic
subtype)
Empirical approach
![Page 57: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/57.jpg)
pH monitoring pH-Impedance
Gastroenterol Clin N Am 2014;43:89–104
![Page 58: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/58.jpg)
pH-impedance monitoring allows identification of subgroups of patients with symptoms that are suspected to be caused by reflux
Gut 2014;63:1185–1193
![Page 59: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/59.jpg)
Approach based on phenotype
Type Interpretation Personal approach
1 GERD • 더 강력한 산분비 억제제
2 정상범위 산역류에 대한 과감각
• Pain modulator (amitryptiline) + (더 강력한) 산분비 억제제
3 산역류가 있으나 그와 무관하게 globus가 있는 경우
• Globus 때문에 산분비 억제제를 쓸 필요는 없음.
• 산역류 증상은 산분비 억제제로 조절
4 GERD 아님 • 산분비 억제제 중단
![Page 60: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/60.jpg)
Refractory GERD의 과거 전략과 신전략
Mori and Suzuki. J Neurogastroenterol Motil 2019;25:6-14
![Page 61: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/61.jpg)
4. PPI의 unmet needs 영역
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
![Page 62: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/62.jpg)
6 1
2 5
4 3
Delayed onset
Poor control of NAB
Poor compliance due to food effect
Enteric coating & Alu/Alu package
Poor PD for H. pylori eradication
High potential of DDI High individual variations PPIs
Major unmet needs of PPIs
![Page 63: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/63.jpg)
Tegoprazan은 PPI의 unmet needs에 대응하는 여러 좋은 특징을 가지고 있음
6 1
2 5
4 3
Fast onset
On demand control of NAB
No food effect
Simple formulation & package
Low potential of DDI Low individual variations
Optimal PD for H.pylori eradication
K-CAB Tegoprazan
![Page 64: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/64.jpg)
Breaktrough symptoms on PPI
![Page 65: Tegoprazan (K-CAB)endotoday.com/endotoday/20190224.pdf · 2019-02-08 · Tegoprazan metabolic pathway - 75% by CYP3A4 2018-9-29. K-CAB conference (신재국) 5. ... (chronic atrophic](https://reader031.fdocuments.net/reader031/viewer/2022012304/5caedb5388c993b41b8cccee/html5/thumbnails/65.jpg)
PPI 사용에도 불구하고 야간 증상을 가진 환자에서 사용할 수 있음
0 2 4 6 8 10 12 14 16 18 20 22 0 2 4 6 8 10 12 14 16 18 20 22
7
6
5
4
3
2
1
2
1
Intr
agas
tric
p
H
Time after dosing (hr)
24
Dosing (IP) Meal Meal Meal
Tegoprazan 50 mg
Dexlansoprazole 60 mg
Baseline
Ref. Clinical study report of [CJ_APA_105] study
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식전 식후 복용할 수 있어 편리하다. On demand therapy에 적용할 수 있다.
5.41 5.71
74.4 85.7
71.1
1) Arithmetic Mean
Ref. Clinical study report of [CJ_APA_102] study
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Simple formulation of K-CAB
Nexium 20 mg 14 mm x 7 mm
Vonoprazan 20 mg 11.2 mm x 6.2 mm
Tegoprazan 50 mg 10.0 mm x 6.8 mm
Nexium 40 mg 16 mm x 8 mm
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Some more comments
성균관대학교 의과대학 삼성서울병원 소화기내과 이준행
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Migrating motor complex (MMC)를 촉진
J Pharmacol Exp Ther. 2018
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Stomach에서의 역할은?
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Gastric ESD의 주된 합병증은 출혈 - ESD 당일 아침 tegoprazan을 한번 먹으면 어떨까?
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다른 P-CAB과의 비교
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새롭고 강력한 위산분비억제제 Tegoprazan의 다양한 (잠재적) 적응증
• Erosive esophagitis의 초치료 및 유지 요법
• Non-erosive reflux disease (NERD) 초치료 유지 요법
• Refractory GERD의 일부 subtype 혹은 경험적 치료
• Long-term treatment with on-demand method
• PPI의 unmet needs에 해당하는 경우
– 야간 증상, 아침 식전 투약이 어려운 경우
– Drug-drug interaction이 우려되는 경우, PPI의 부작용
– Rapid metabolizer, Clopidogrel 복용자
– Helicobacter 제균치료
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K-CAB: Fast, Strong and Long