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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 (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]

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.

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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

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★リンクテーブル★

リンク元	「H2受容体拮抗薬」「ラフチジン」

「H2受容体拮抗薬」

Lafutidine
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
KEGG	D01131
Chemical data
Formula	C22H29N3O4S
Mol. mass	431.54 g/mol
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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

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H2受容体拮抗薬 : 約 249,000 件
H2受容体遮断薬 : 約 24,400 件

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消化性潰瘍治療薬
命名法は" -tidine"
特徴

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)