ラフチジン
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/02/02 23:03:16」(JST)
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Lafutidine
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Systematic (IUPAC) name |
2-[(2-furylmethyl)sulfinyl]-N-((2Z)-4-{[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxy}but-2-en-1-yl)acetamide |
Clinical data |
AHFS/Drugs.com |
International Drug Names |
Pregnancy cat. |
? |
Legal status |
? |
Routes |
Oral |
Identifiers |
CAS number |
118288-08-7 |
ATC code |
A02BA08 |
PubChem |
CID 5282136 |
UNII |
49S4O7ADLC Y |
KEGG |
D01131 Y |
Chemical data |
Formula |
C22H29N3O4S |
Mol. mass |
431.54 g/mol |
Y (what is this?) (verify)
|
Lafutidine (INN) is a second generation H2 receptor antagonist having multimodal mechanism of action. It is currently marketed in Japan (Stogar) [1] China (Lemeiting) [2] and India (Lafaxid) [3] It not only suppresses gastric acid secretion, but also has cytoprotective properties by the virtue of its property to induce the collagen synthesis in the gastric mucosa.[4] It has a novel mechanism of action in addition to blocking the H2 receptors , it decreases inflammation by modulating Capsaicin- sensitive gene-related peptide (CGRP) [5] and vanilloid receptors [6] It is also found to stimulate mucin biosynthesis and promote the restitution of damaged mucosa.[7]
Contents
- 1 Mechanism of Action
- 1.1 Acid Suppressive action
- 1.2 Gastroprotective action
- 2 Pharmacokinetics
- 3 Adverse effects
- 4 References
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Mechanism of Action
Acid Suppressive action
Lafutidine is absorbed in the small intestine, reaches gastric cells via the systemic circulation, and then directly and rapidly binds to gastric cell histamine H2 receptors, thereby inhibiting the stimulation of cAMP and a resultant decrease in acid production (antisecretory action).[8] It causes a sustained increase in intracellular Ca2+ ion concentration in endothelial cells resulting in the release of Calcitonin Gene Related Peptide (CGRP), which causes acid suppression by decreasing the vagal tone.[9] Lafutidine also increases plasma somatostatin levels which decreases secretion of gastrin from G cells. This decrease in gastrin causes inhibition of parietal cells, resulting in decrease in gastric acid secretion.[10][11]
Gastroprotective action
Lafutidine induced CGRP release stimulates nitric oxide (NO) production in endothelial cells, where NO participates in the regulation of gastric mucosal blood flow through vasodilation in the gastric microvasculature and increases mucin biosynthesis resulting in gastroprotection.[12][13] Lafutidine inhibits secretion of interleukin-8, which in turn inhibits sequestration of neutrophils at the site of inflammation, thereby preventing mucosal inflammation [14] It also inhibits neutrophil activation which reduces damage caused by free radicals, thereby reducing inflammation [5] Additionally, Lafutidine has been found to block the attachment of H. pylori with the gastric cells, thereby preventing diseases like peptic ulcer.[14]
Pharmacokinetics
When 10 mg of lafutidine was orally administered to healthy adult males in fasting conditions, peak plasma concentration of 265.15 ± 49.84 ng/ml was achieved at 0.95 ± 0.24 hours. The plasma half life was 1.92 ± 0.94 hours.[15] Among the elderly, there was no difference in pharmacokinetics parameters between those with normal renal function (Ccr average 88.0±9.4 mL/min) and those with deteriorating renal function (Ccr 20~60ml/min, average 45.2±7.8 ml/min).[14] In dialytic patients when administered without hemodialysis, the Cmax, AUC and the t1/2 values were 336±40 ng/ml, 2278±306 ng.hr/mL and 6.71±0.30 hours respectively while those after hemodialysis were 226±36 ng/ml, 853±128 ng.hr/mL and 4.57±0.2 hours respectively.[16] Therefore lafutidine should be administered carefully with lower dosage in dialytic patients.
Adverse effects
Antacid preparations such as lafutidine by suppressing acid mediated break down of proteins, leads to an elevated risk of developing food or drug allergies. This happens due to undigested proteins then passing into the gastrointestinal tract where sensitisation occurs. It is unclear whether this risk occurs with only long-term use or with short-term use as well.[17]
References
- ^ Stogar tablets, UCB Japan, Japan.
- ^ Lemeiting tablets,Sibao Pharmaceutical, China.
- ^ Lafaxid tablets, Zuventus Healthcare Ltd. India
- ^ Y.Fukushima, H. Otsuka, M. Ishikawa et al. (2001) Potent and long-lasting action of Lafutidine on the human histamine H(2) receptor, Digestion, Vol. 64, No. 3, pp: 155-60
- ^ a b N. Harada, K. Okajima et al. (2007) Inhibition of neutrophil activation by Lafutidine, an H2-receptor antagonist, through enhancement of sensory neuron activation contributes to the reduction of stress-induced gastric mucosal injury in rats, Dig Dis Sci, Vol. 52, No. 2, pp: 469-77
- ^ T. Sugiyama, Y. Hatanaka, Y. Iwatani et al. (2008) Lafutidine facilitates calcitonin gene-related peptide (CGRP) nerve-mediated vasodilation via vanilloid-1-receptors in rat mesenteric resistance arteries, J Pharmacol Sci, Vol. 106, No. 3, pp: 505-11
- ^ Y. Nozawa, K. Nishihara, Y. Akizawa et al. (2004) Lafutidine inhibits Helicobacter pylori- induced interleukin-8 production in human gastric epithelial cells, J Gasteroenterol Hepatol, Vol. 19, No. 5, pp: 506-11
- ^ Kazuro et al. Pharmacokinetic and Pharmacodynamic Properties of Lafutidine after Postprandial Oral Administration in Healthy Subjects: Comparison with Famotidine. Biol. Pharm. Bull., 2007; 30: 1003-1006.
- ^ Kunieda et al. Lafutidine-Induced Increase in Intracellular Ca2+ Concentrations in PC12 and Endothelial Cells. J. Pharmacol. Sci., 2005; 97: 67-74
- ^ Inamori et al. Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use? J. Gastroenterol., 2005; 40: 453-458
- ^ Itoh et al. Lafutidine changes levels of somatostatin, calcitonin gene-related peptide, and secretin in human plasma. Biol. Pharma. Bull., 2002; 25: 379-382
- ^ Chen RYZ, Guth PH. Interaction of endogenous nitric oxide and CGRP in sensory neuron-induced gastric vasodilation. Am. J. Physiol., 1995; 268: G791-G796
- ^ Ichikawa et al. Lafutidine induced stimulation of mucin biosynthesis mediated by nitric oxide is limited to surface mucous cells of rat gastric oxyntic mucosa. Life Sci., 1998, 62:259.264
- ^ a b c Nozawa et al. Lafutidine inhibits Helicobacter pylori- induced interleukin-8 production in human gastric epithelial cells. J Gasteroenterol Hepatol, 2004, 19:506-511
- ^ Haruki, S.et al.:BasicPharmacol. Ther., 23: 3049, 1995
- ^ UCB Japan Co. Ltd., STOGAR Tablet, Prescribing Information
- ^ Pali-Schöll I, Jensen-Jarolim E (April 2011). "Anti-acid medication as a risk factor for food allergy". Allergy 66 (4): 469–77. doi:10.1111/j.1398-9995.2010.02511.x. PMID 21121928.
Histaminergics
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Receptor |
H1
|
- Agonists: 2-Pyridylethylamine
- Betahistine
- Histamine
- HTMT
- UR-AK49
Antagonists: 1st generation: 4-Methyldiphenhydramine
- Alimemazine
- Antazoline
- Azatadine
- Bamipine
- Benzatropine/Benztropine
- Bepotastine
- Bromazine
- Brompheniramine
- Buclizine
- Captodiame
- Carbinoxamine
- Chlorcyclizine
- Chloropyramine
- Chlorothen
- Chlorphenamine
- Chlorphenoxamine
- Cinnarizine
- Clemastine
- Clobenzepam
- Clocinizine
- Cyclizine
- Cyproheptadine
- Dacemazine
- Deptropine
- Dexbrompheniramine
- Dexchlorpheniramine
- Dimenhydrinate
- Dimetindene
- Diphenhydramine
- Diphenylpyraline
- Doxylamine
- Embramine
- Etodroxizine
- Etybenzatropine/Ethylbenztropine
- Etymemazine
- Flunarizine
- Histapyrrodine
- Homochlorcyclizine
- Hydroxyethylpromethazine
- Hydroxyzine
- Isopromethazine
- Isothipendyl
- Meclozine
- Mepyramine/Pyrilamine
- Mequitazine
- Methafurylene
- Methapyrilene
- Methdilazine
- Moxastine
- Niaprazine
- Orphenadrine
- Oxatomide
- Oxomemazine
- Phenindamine
- Pheniramine
- Phenyltoloxamine
- Pimethixene
- Piperoxan
- Pipoxizine
- Promethazine
- Propiomazine
- Pyrrobutamine
- Talastine
- Thenalidine
- Thenyldiamine
- Thiazinamium
- Thonzylamine
- Tolpropamine
- Tripelennamine
- Triprolidine
- 2nd generation: Acrivastine
- Alinastine
- Astemizole
- Azelastine
- Bamirastine
- Barmastine
- Bepiastine
- Bepotastine
- Bilastine
- Cabastinen
- Carebastine
- Cetirizine
- Clemastine
- Clemizole
- Clobenztropine
- Dorastine
- Ebastine
- Emedastine
- Epinastine
- Flezelastine
- Ketotifen
- Latrepirdine
- Levocabastine
- Linetastine
- Loratadine
- Mapinastine
- Mebhydrolin
- Mizolastine
- Moxastine
- Noberastine
- Octastine
- Olopatadine
- Perastine
- Piclopastine
- Rocastine
- Rupatadine
- Setastine
- Talastine
- Temelastine
- Terfenadine
- Zepastine
- 3rd generation: Desloratadine
- Fexofenadine
- Levocetirizine
- Ungrouped: Belarizine
- Efletirizine
- Elbanizine
- Flotrenizine
- Medrylamine
- Napactadine
- Pibaxizine
- Tagorizine
- Trelnarizine
- Trenizine
- Vapitadine
- Miscellaneous: Tricyclic antidepressants (amitriptyline,
- doxepin,
- trimipramine, etc)
- Tetracyclic antidepressants (mianserin,
- mirtazapine, etc)
- Typical antipsychotics (chlorpromazine,
- thioridazine, etc)
- Atypical antipsychotics (clozapine,
- olanzapine,
- quetiapine, etc)
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H2
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- Agonists: Amthamine
- Betazole
- Dimaprit
- Histamine
- HTMT
- Impromidine
- UR-AK49
Antagonists: Bisfentidine
- Burimamide
- Cimetidine
- Dalcotidine
- Donetidine
- Ebrotidine
- Etintidine
- Famotidine
- Lafutidine
- Lamtidine
- Lavoltidine/Loxtidine
- Lupitidine
- Metiamide
- Mifentidine
- Niperotidine
- Nizatidine
- Osutidine
- Oxmetidine
- Pibutidine
- Quisultazine/Quisultidine
- Ramixotidine
- Ranitidine
- Roxatidine
- Sufotidine
- Tiotidine
- Tuvatidine
- Venritidine
- Xaltidine
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H3
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- Agonists: α-Methylhistamine
- Cipralisant
- Histamine
- Imetit
- Immepip
- Immethridine
- Methimepip
- Proxyfan
Antagonists: A-349,821
- A-423,579
- ABT-239
- Betahistine
- Burimamide
- Ciproxifan
- Clobenpropit
- Conessine
- GSK-189,254
- Impentamine
- Iodophenpropit
- JNJ-5,207,852
- MK-0249
- NNC-38-1,049
- PF-03654746
- Pitolisant
- SCH-79,687
- Thioperamide
- VUF-5,681
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H4
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- Agonists: 4-Methylhistamine
- Histamine
- VUF-8,430
Antagonists: JNJ-7,777,120
- Thioperamide
- VUF-6,002
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|
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Transporter |
VMAT
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- Inhibitors: Ibogaine
- Reserpine
- Tetrabenazine
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Enzyme |
HDC
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- Inhibitors: Catechin
- Meciadanol
- Naringenin
- Tritoqualine
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DAO
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- Inhibitors: Aminoguanidine
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|
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Others |
Endogenous
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- Histamine; Precursors: L-Histidine; Cofactors: Vitamin B6
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Drugs for acid related disorders: Drugs for peptic ulcer and GERD/GORD (A02B)
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H2 antagonists ("-tidine") |
- Cimetidine
- Famotidine
- Lafutidine
- Loxtidine
- Niperotidine
- Nizatidine
- Ranitidine
- Roxatidine
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Prostaglandins (E)/analogues ("-prost-") |
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Proton-pump inhibitors ("-prazole") |
- Dexlansoprazole
- Esomeprazole
- Ilaprazole
- Lansoprazole
- Omeprazole
- Pantoprazole
- Rabeprazole
- Tenatoprazole
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Other |
- Acetoxolone
- Alginic acid
- Carbenoxolone
- Cetraxate
- Gefarnate
- Pirenzepine
- Telenzepine
- Proglumide
- Sucralfate
- Sulglicotide
- Teprenone
- Troxipide
- Zolimidine
- Rebamipide
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- See also: Helicobacter pylori eradication protocols
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anat (t, g, p)/phys/devp/enzy
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noco/cong/tumr, sysi/epon
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proc, drug (A2A/2B/3/4/5/6/7/14/16), blte
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English Journal
- Lafutidine, a unique histamine H2-receptor antagonist, inhibits distention-induced gastric acid secretion through an H2 receptor-independent mechanism.
- Nakano M, Kitano S, Nanri M, Kiniwa M.SourceDepartment of Applied Pharmacology, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima, 771-0194, Japan. moto-nakano@taiho.co.jp
- European journal of pharmacology.Eur J Pharmacol.2011 May 11;658(2-3):236-41. Epub 2011 Feb 22.
- Gastric acid secretion during the daytime has been implicated in the pathogenesis of acid-related diseases. Although daytime acid secretion is mainly governed by the parasympathetic vagal nerve, clinical observations have been accumulated that the H(2)-receptor antagonist lafutidine may have a stron
- PMID 21349265
- Lafutidine 10 mg versus Rabeprazole 20 mg in the Treatment of Patients with Heartburn-Dominant Uninvestigated Dyspepsia: A Randomized, Multicentric Trial.
- Dewan B, Philipose N.SourceMedical Services Department, Zuventus Healthcare Ltd, 5119 "D" Wing, Oberoi Garden Estate, Chandivilli, Mumbai 400072, India.
- Gastroenterology research and practice.Gastroenterol Res Pract.2011;2011:640685. Epub 2011 May 5.
- Background. Empirical therapy with antisecretory agents like PPIs and H2RAs has long been the traditional approach in the initial management of uninvestigated dyspepsia. Aim. The objective of the study was to examine relief of dyspepsia with lafutidine, a second-generation H(2)-RA, and rabeprazole a
- PMID 21687618
- Early effects of oral administration of lafutidine with peppermint oil, compared with lafutidine alone, on intragastric pH values.
- Iida H, Inamori M, Uchiyama T, Endo H, Hosono K, Akiyama T, Sakamoto Y, Fujita K, Takahashi H, Yoneda M, Koide T, Tokoro C, Goto A, Abe Y, Kobayashi N, Kirikoshi H, Kubota K, Saito S, Nakajima A.SourceGastroenterology Division, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.
- Hepato-gastroenterology.Hepatogastroenterology.2011 Jan-Feb;58(105):235-8.
- BACKGROUND/AIMS: Ideally, medications for the treatment of acid-related diseases should have a rapid onset of action to promote hemostasis and the resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of lafut
- PMID 21510321
Japanese Journal
- 軽症逆流性食道炎に対するプラセボおよびファモチジンを対照としたラフチジンの有効性の検討 : 実施担当医師と内視鏡判定委員会の写真判定の比較検討を含めて
- 大原 秀一,春間 賢,木下 芳一,草野 元康
- 日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 107(4), 588-597, 2010-04-05
- 軽症逆流性食道炎に対するラフチジンの有効性を,ファモチジンおよびプラセボを対照薬とした多施設共同,二重盲検比較試験で検討した.内視鏡写真判定は実施担当医師および内視鏡判定委員会でそれぞれ実施した.内視鏡判定委員会判定ではラフチジン,ファモチジン,プラセボの8週治癒率は67.7%(65/96),61.2%(60/98),41.2%(21/51)でありラフチジンの治癒率はプラセボの治癒率よりも有意に高 …
- NAID 10026417098
- Lafutidine Facilitates Calcitonin Gene-Related Peptide (CGRP) Nerve-Mediated Vasodilation via Vanilloid-1 Receptors in Rat Mesenteric Resistance Arteries
- SUGIYAMA Tetsuhiro,HATANAKA Yukako,IWATANI Yukiko,JIN Xin,KAWASAKI Hiromu
- Journal of pharmacological sciences 106(3), 505-511, 2008-03-20
- … Lafutidine is a histamine H2-receptor antagonist with gastric antisecretory and gastroprotective activity associated with activation of capsaicin-sensitive nerves. … The present study examined the effect of lafutidine on neurotransmission of capsaicin-sensitive calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRPergic nerves) in rat mesenteric resistance arteries. …
- NAID 10024319549
Related Links
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- のサプライヤーのリストを取得する Lafutidine と同等の製品を ... Chemos GmbH ためのサプライヤです Lafutidine. 我々としても(4-Pentenyl)triphenylphosphoniumbromideを販売しています。 Chemosは、化学、生化学、実験装置の世界的な ...
Related Pictures
★リンクテーブル★
[★]
- 英
- H2 blocker H2-blockers
- 同
- H2受容体ブロッカー H2 receptor blocker、H2受容体拮抗薬 H2 receptor antagonist H2RA、ヒスタミンH2受容体遮断薬 ヒスタミンH2受容体拮抗薬 histamine H2-receptor antagonists histamine H2 receptor antagonist histamine H2 antagonist、H2拮抗薬 H2 antagonist H2-antagonist、H2遮断薬、H2ブロッカー
- 関
- 抗ヒスタミン薬
[show details]
GOO.chapter36 p.971
- 十二指腸潰瘍の治癒率を向上する (⇔プロトンポンプ阻害薬)
H2受容体拮抗薬
構造
作用機序
- H1受容体にはほとんど作用しない
- H2受容体に可逆的、競合的に結合してヒスタミンを阻害する。
- 胃粘膜の局所の肥満細胞、ECL細胞
- histamine→H2R→Csα→AC→cAMP↑→PKA→H+,K+-ATPase
- histamine→H2R→[Ca2+]i↑→H+,K+-ATPase ←補助的pathway
- H2RとMRとGRは相互作用しており、胃酸を分泌する。
注意
- 中止すると再発率が高い。そのため半年かけて漸減させゆっくり離脱
- 胃粘膜が減弱している
副作用
- 副作用5%↓
- 汎血球減少症、無顆粒球症
- 肝障害、抗アンドロゲン作用(女性化乳房、乳汁分泌)
- 中止すると再発率が高い。そのため半年かけて漸減させゆっくり離脱
- 胃粘膜が減弱しているから
相互作用
- シメチジン:CYP2D6, CYP3A4阻害作用。 CYPs(CYP1A2,CYP2C9,CYP2D6)の阻害 (GOO.972)
- ラニチジン:CYPs。しかし、シメチジンの10%程度
- ファモチジン、ニザチジン:なし
[★]
- 英
- lafutidine
- 商
- プロテカジン、ストガー
- 関
- ヒスタミン受容体
-
- H2 blocker + カプサイシン感受性視覚神経を介した胃粘膜防御因子・増強因子
- 腎機能による用量調節が不要と言われている
- 用量
- 胃潰瘍、十二指腸潰瘍、吻合部潰瘍、逆流性食道炎:1回10mgを1日2回(朝食後、夕食後または就寝前)
- 急性胃炎、慢性胃炎の急性増悪期による胃粘膜病変(びらん、出血、発赤、浮腫)の改善:1回10mgを1日1回(夕食後または就寝前)経口投与
- 麻酔前投薬:1回10mgを手術前日就寝前及び手術当日麻酔導入2時間前の2回経口投与