英文药名：PROTECADIN tablet（Lafutidine）

中文药名：拉呋替丁片

生产厂家：大鹏药业有限公司
药品介绍
拉呋替丁是日本富士（ Fujirebio）公司和大鹏（Taiho）公司联合开发的一种抗溃疡药，该产品为强效、长效的第二代组胺H2受体拮抗剂，具有独特的胃保护作用。已于2000年4月在日本上市。
本品为第二代H2受体拮抗剂，主要用于治疗消化性溃疡，本品可减少胃酸的基础分泌量，抑制组胺、胃泌素、乌拉坦刺激的胃酸分泌。
相比其它同类药物（如西咪替丁和法莫替丁），本品对H2受体的阻断作用更有效、持久，所以具有抗胃酸分泌作用更加持续的优点。胃溃疡和十二指肠溃疡 。
药理作用
拉呋替丁能持续地抑制人胃酸、胃蛋白酶的基础分泌、夜间分泌及四肽胃泌素等刺激因子引起的分泌，对胃酸的抑制作用与法莫替丁和西咪替丁相比，作用更有效、更持久。
拉呋替丁还具有很强的黏膜保护作用，在低于抗胃酸分泌剂量下就可产生抗溃疡活性。而法莫替丁和西咪替丁只有在高于抗分泌剂量下才能发挥抗溃疡活性。
动物实验中，拉呋替丁可使胃黏膜损伤加速愈合，包括恢复变薄的胃黏膜厚度和减少的壁细胞数量，而法莫替丁和西咪替丁在产生相同程度的抗胃酸分泌作用的同时没有这些形态学作用。以奥美拉唑为代表的现有的质子泵抑制剂也无胃黏膜保护作用。
另外，接受拉呋替丁治疗后的复发率低。与法莫替丁和雷尼替丁在实验性胃溃疡愈合率相当的剂量下，三者的溃疡复发率分别为4%、40.9%和31.3%，拉呋替丁与后二者差异有显着性。
临床作用
1) 治疗消化性溃疡
临床试验中，采用多中心、随机、双盲、阳性药物平行对照的临床研究。对不同中心进行区组随机分配，分为两组，一组为试验药拉呋替丁片，另一组为对照药法莫替丁片。
本试验共入组患者207例，拉呋替丁组103例，法莫替丁组104例，全部患者均使用了研究药物并进行了至少一次安全性评价和有效性评价，202例被纳入PPS分析，其中拉呋替丁组102例，法莫替丁组100例，所有入组患者被纳入FAS分析与安全性分析数据集（SS）分析；试验中有5例患者脱落，脱落率为2.42%。无剔除病例。
内镜检查溃疡愈合率：PPS人群中拉呋替丁组溃疡愈合率为85.1%,法莫替丁组溃疡愈合率为75%，两组溃疡治愈率差异无显着性（P>0.05）。总有效率：PPS人群中拉呋替丁组溃疡总有效率为93.1%,法莫替丁组溃疡总有效率为82%，两组总有效率差异有显着性（P<0.05）。
2) 治疗急性胃炎
临床报道，在治疗急性胃炎时，服用拉呋替丁10mg/次，2次/d，连续用药6天，结果治愈率为96.8%。机制：胃炎急性期胃黏膜充血、水肿、胃酸分泌过多等造成一系列临床刺激症状，应用拉呋替丁将H2受体阻断，减少胃酸分泌，控制和改善黏膜充血、水肿，使疼痛、恶心及呕吐症状消失。
3) 在胃泌素瘤中的应用
胃泌素瘤好发于十二指肠和胰腺，亦可见于脾门、胃或肝脏，高胃泌素血症是诊断胃泌素瘤有价值的依据之一。大多数胃泌素瘤病人未刺激胃酸分泌超过18mmol/L。拉呋替丁是被证明治疗胃泌素瘤有效的H2受体阻断剂，可缓解症状、减少酸分泌和治疗溃疡。拉呋替丁经安全性评价，均未证明有致癌性、致突变性和致畸性。
根据临床观察，本药不良反应甚微，少数患者有口干、头晕、失眠、便秘、腹泻等症状。
包装
プロテカジン錠 5　
PTP包装：100錠（10錠×10）、1000錠（10錠×10×10）

プロテカジン錠10　
PTP包装：100錠（10錠×10）、1000錠（10錠×10×10）、1400錠（14錠×10×10）　
バラ包装：500錠

制造厂商
大鹏药业有限公司

原研药品资料附件：http://www.info.pmda.go.jp/go/pack/2325006F1036_1_16/
Name of drug classification
H2 receptor antagonist
Sales name
Procaskin tablet 5
Common name
Lafutidine
Chemical name
(±) -2- (Furfurylsulfinyl) -N- [4- [piperidinomethyl) -2-pyridyl] oxy- (Z) -2-butenyl] acetamide
Molecular formula
C22H29N3O4S
Molecular weight
431.55
Melting point
96 ~ 99 ℃
Partition coefficient (log P)
-3.36 (pH 2), 0.39 (pH 6), 2.37 (pH 10)
(1-octanol / Britton-Robinson Buffer (20 ± 1 ° C.))
Property
It is a slightly yellowish crystalline powder with a slightly peculiar smell. It is easily soluble in acetic acid (100), slightly soluble in methanol, slightly soluble in ethanol (99.5), very insoluble in diethyl ether, and hardly soluble in water. The methanol solution (1 → 100) shows no optical rotation.
composition
Component · Content
Lafutidine in 1 tablet 5 mg
Additive
Lactose hydrate, crystalline cellulose, corn starch, croscarmellose sodium, hydroxypropyl cellulose, hypromellose, light anhydrous silicic acid, talc, magnesium stearate, titanium oxide, macrogol 6000, carnauba wax
Contraindications
Patients with a history of hypersensitivity to the ingredients of this drug
Indication or effect
○ gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis
○ Improvement of gastric mucosal lesions (erosion, bleeding, redness, edema) of the following diseases
Acute gastritis, acute exacerbation phase of chronic gastritis
○ Pre-anesthesia medication
The efficacy and safety of severe (Los Angeles classification Grade C or D) for reflux esophagitis has not been established.
○ gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis
Usually, adults are orally administered 10 mg once a day (after breakfast, after dinner or before going to bed) as lafutidine. Incidentally, it increases and decreases according to age and symptoms as appropriate.
○ Improvement of gastric mucosal lesions (erosion, bleeding, redness, edema) of the following diseases
Acute gastritis, acute exacerbation phase of chronic gastritis
Normally, adults are orally administered with 10 mg once a day (after dinner or before going to bed) as lafutidine. Incidentally, it increases and decreases according to age and symptoms as appropriate.
○ Pre-anesthesia medication
Normally, adults are orally administered with 10 mg once a day as raftidine twice a day before sleeping on the day before surgery and 2 hours before introduction of anesthesia on the day of surgery.
For dialysis patients, it is reported that the maximum blood concentration at non-dialysis rose about twice as high as that of healthy people, so careful administration should be made from low dose (see "Pharmacokinetics").
Careful Administration
Patients with a history of drug hypersensitivity
Patients with hepatic impairment [Symptoms may worsen]
Patients with renal impairment [Symptoms may worsen]
Dialysis patient [Increase in blood concentration has been reported (see "Pharmacokinetics")]
Elderly (see "Administration to the elderly" section)
Serious side effects
[Frequency of expression unknown]
Shock, anaphylactoid symptoms
Shock and anaphylactoid-like symptoms may occur, so observe thoroughly and if face pallor, blood pressure decrease, whole body redness, dyspnoea etc. appears, discontinue administration and take appropriate measures.
Liver dysfunction
Liver dysfunction accompanied by elevated AST (GOT), ALT (GPT), γ-GTP etc., jaundice may occur, so observe thoroughly and if abnormality is found discontinue administration and appropriate Take action.
Agranulocytosis, thrombocytopenia
Since nonagranulocytosis (initial symptoms: sore throat, general malaise, fever etc.) and thrombocytopenia may occur, if abnormalities are observed discontinue administration and take appropriate measures.
Medicinal pharmacology
Action in humans
Basal and various stimulus gastric acid secretion
In healthy adults, gastric acid secretion for 2 hours at the time of administration of basal, tetragastrin stimulant and betazole hydrochloride stimulant was 95.1%, 84.0%, 98.3%, pectin secretion was 69.2%, 46.0% by oral administration of 10 mg, respectively, It was suppressed by 86.8%.
Nocturnal gastric acid secretion
Gastric acid secretion and pepsin secretion of healthy adults from 11 pm to 6 am were suppressed by 95.6% and 57.9% by oral administration of 10 mg, respectively.
24-hour gastric pH monitor
In healthy adults, 10 mg oral administration before going to bed, the intragastric pH became pH 5 or more after 2 hours of administration, the pH remained in the range of 6 to 7 until 10 hours, and the ratio of holding time of pH 3 or more in the nighttime 12 hours It was 75.0%. In addition, it was 67.8% and 60.2% in the nighttime and 12 hours during the day by oral administration of 10 mg twice a day, respectively, and gastric acid secretion was inhibited during the day as well as at night.
Gastric mucus increasing action
In healthy adults, oral administration of 10 mg twice a day for 3 days for 3 days resulted in a significant increase in the amount of hexosamine in gastric juice at 1 to 1.5 hours after administration compared to placebo administration. In patients who are scheduled to undergo gastrectomy, oral administration of 10 mg twice a day for 2 weeks, the amount of mucin in the mucous gel layer of the excised stomach body increased about three times that of non-administration.
The gastric mucosal blood flow increasing effect is not clinically proven.
Action in animals
Suppression of gastric acid secretion
The effect of suppressing gastric acid secretion 4 hours after ligating the pylorus and various drugs into the duodenum was 0.1 times that of famotidine and 2.3 times that of cimetidine (rat). However, gastric acid secretion inhibitory action by various stimulants persisted more than famotidine and cimetidine (rat, dog).
H2 receptor antagonism
The inhibitory action of thiotidine on the specific binding by the guinea pig cerebral cortex membrane was 1.9 times that of famotidine and 85.5 times that of cimetidine (in vitro).
Action on acute gastric mucosal lesions
It showed gastric mucosal protection against gastric mucosal damage caused by various necrosis substances (ammonia, hydrochloric acid • ethanol, ethanol, hydrochloric acid, hydrochloric acid • taurocholic acid). In particular, it showed a strong protective effect against ammonia damage (rat).
Action on acute / chronic ulcer
Inhibition of the occurrence of acute gastric ulcer (water immobilized stress, indomethacin, pylorus ligation aspirin, histamine) or acute duodenal ulcer (mepirizole, diethyl dithiocarbamate), also promoting healing promotion against chronic ulcers (acetic acid ulcer, cauterized ulcer) It showed recurrence-suppressing effect (rat).
Effect on gastritis
It showed a recovery promoting effect against gastritis caused by ammonia and taurocholic acid (rat).
Action on acute reflux esophagitis
Prevents the occurrence of esophageal mucosal lesion caused by forestomach-pylorus ligation (rat).
Gastric mucosal blood flow increasing effect 32)
Intragastric administration showed an incremental blood flow increasing effect (rat).
Increase in gastric mucus 33 ~ 35)
Promotes mucus production in organ culture of rat gastric mucosa (in vitro). In addition, oral administration increased the amount of mucin in the gastric mucosal gel layer, and further continuous administration showed a tendency of increasing the gel layer in the pyloric gland region (rat).
Mucosal reconstruction promoting action
As a result of examining the repair process of gastric mucosal damage caused by ammonia at the coverage of AB staining positive cells, the ratio was raised from 30 minutes later and showed a reconstitution promoting effect by epithelial cell migration (rat).