Helicobacter pyloir 양성 소화성 궤양에서 lansoprazole 포함 삼제요법의 제균율 및 제균판정에 있어서 요소호기검사의 유용성

정혜경,곽재진,유민아,배기선,권정미,이종수,김도영,문일환 대한감염학회 2003 감염과 화학요법 Vol.35 No.3

목적 : 본 연구는 Helicobacter pylori (이하 H. polyri) 양성인 소화성 궤양 환자에서 lansoprazole 포함 삼제요법의 제균율을 알아보고, 제균 치료 후 제균 판정에 있어서 요소 호기 검사(Urea breath test, 이하 UBT) 및 신속요소분해(rapid urease test, 이하 RUT test)와의 일치율에 대하여 알아보고자 하였다. 방법 : 상부위장관내시경 검사에서 H. polyri 양성인 소화성 궤양환자에서 lansoprazole 60㎎+amoxicillin 2g+clarithromycin 1g의 약제를 2회 분복하여 1주간 복용하는 삼제요법을 실시하였다. 최소 4주후 추적 상부위장관내시경을 실시하였고, 전정부와 체부에서 각각 RUT를 실시하였으며 UBT(5분, 20분)를 시행하였다. 결과 : 대상환자는 총 46명으로 남자 34명(48±13세), 여자 12명(53±14세)이었다. LAC 삼제요법의 제균율은 40/46명(87.0%)이었고, 궤양의 치유율도 42/46명(91.3%)이었다. RUT와 20분 UBT 결과가 모두 음성이었던 경우는 41예, 모두 양성이었던 경우는 4예로 RUT와 UBT는 97.8% (45/46)의 일치율을 보였고, 1예는 UBT는 음성이었으나 체부에서 시행한 RUT가 양성이었다. 5분 UBT 검사가 양성이었던 예는 14/34 (41.2%) 이었고, 이 14예 중 12예(85.7%)는 20분 UBT 검사 음성, RUT 음성이었다. 결론 : Lansoprazole과 amoxicillin, clarithromycin 1주일 병합요법은 H. polyri 양성인 소화성 궤양 환자에서 87.0%의 제균율을 나타내어 우수한 효과를 보였고, 요소호기검사는 제균 치료 후 제균 판정에 유용한 비침습적인 방법임을 확인할 수 있었다. Background : There are only a few studies on Helicobacter pylori (H. pylori) for its eradication rates of lansoprazole-based triple therapy in Korea, and the results are controversial. Therefore, we undertook to investigate the eradication rate of lansoprazole-based triple therapy, and compare the concordance rate of urea breath test (UBT) and rapid urease test (RUT) in evaluating H. pylori eradication. Methods : Patients with acute peptic ulcer who were H. pylori-positive were recruited by prospective, consecutive manner. They received lansoprazole 30 ㎎ b.d., amoxicillin 1 g b.d. and clarithromycin 500 ㎎ b.d. for 1 week. Upper endoscopy was performed after 4 weeks to check for ulcer healing, and UBT and RUT were performed to evaluate H. pylori eradication status. Results : A total of 46 patients were recruited, and they were all compliant. H. pylori eradication rate was 87.0% (40/46) and ulcer healing rate was 91.3% (42/46). Forty one patients showed negative in both UBT and RUT, and 4 patients revealed positive in both tests, therefore, the concordance rate of UBT and RUT was 97.8% (45/46). Conclusion : Our study showed that 1-week lansoprazole-based triple therapy was effective in H. pylori eradication and ulcer healing. UBT can be an effective, noninvasive method for evaluating H. pylori status after H. pylori eradication.

알긴산 나트륨이 장용코팅된 란소프라졸 제제의 저장안정성 및 용출률에 미치는 영향에 관한 연구

김정훈,오정민,강길선,정제교,이정식,정상영,이해방 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.4

Lansoprazole, pharmaceutics for acid-related diseases, is unstable in low pH environments and generally coated with enteric polymer to obtain gastroresistance in stomach. Because its storage stability is influenced by acidic substitutes of enteric polymer, alkaline chemicals were generally added to dosage form as a stabilizer. In this experience, we coated lansoprazole bead with sodium alginate and evaluated the effect of bead size and sodium alginate coating on the storage stability and dissolution profile of lansoprazole. Sodium alginate solution containing lansoprazole was sprayed as a droplet into 3% (w/v) CaCl_2 solution and the resultant bead was coated with starch, sodium alginate, and hydroxypropyl methylcellulose phthalate. The content of lansoprazole granule not coated with sodium alginate decreased to 57.96% of initial content when stored at a severe condition for 4 weeks, but that of lansoprazole granule coated with sodium alginate before enteric coating decreased little and as the thickness of sodium alginate film increased, the content of bead didn't decreased for 4 weeks. Sodium alginate film also improved the gastroresistance without much influencing the maximum dissolution rate.

위, 십이지장궤양에 대한 Lansoprazole의 치료효과

윤종만,최성규,류도현,한상우,유종선,김영진,범희승 최신의학사 1996 最新醫學 Vol.39 No.1

장용성 란소프라졸 캅셀의 제조 및 생물학적 동등성 시험

박경호,남궁형욱,신완균 한국병원약사회 1997 병원약사회지 Vol.14 No.3

Iansoprazole, (H+/K+)-ATPase (proton pump) inhibitor is being widely used to gastro-intestinal peptic ulcer patients. Koryo Pharmaceutical Company tried to develope lansoprazole capsule bioeqivalent to already being marketed lansoprazole capsule, reference product, which is producted by Hanil Pharmaceutical Company. Through in vitro dissolution tests of preformulated test capsules (Test capsule A, B, C and D) compared with reference, one capsule (Test capsule D) compared with reference, one capsule (Test capsule D) was selected which had a very similar dissolution profile as reference. And bioequivalence test in human volunteers was conducted to obtain marketing approvement of test capsule D. Dissolution tests of preformulated products were conducted in dissolution solution I (acid solution, pH 1.2) by dissolution method Ⅱ(paddle method) (KP Ⅵ) for 60 minutes, and then followed in dissolution solution Ⅱ(phosphate buffer, pH 6.8) by dissolution method Ⅰ (basket method) (KP Ⅵ) for 60 minutes. The dissolution solutions was maintained at 37±0.5℃, and basket and paddle were rotated at 150± 5 rpm, respectively. Also, in bioequivalence test, 14 healthy male volunteers were administered one capsule of test capsule(30 ㎎ lansoprazole/cap, Koryo Pharm. Co.) or reference, and randomized two-period, cross-over study was applied. Bioequivalence was statistically analyzed between two products using pharmacokinetic parameters (AUC, C_(max) and T_(max)). The results showed that the differences in AUC, C_(max) and T_(max) between two products were 8.75%, 9.32% and 29.79%, respectively. Detectable (△) of AUC, C_(max) ands T_(max) were 15.79%, 18.18% and 45.17%, at α=0.1 and power (1-β)=0.8, respectively, and also confidence intervals were -1.91% ≤△≤ 19.41%, -2.96% ≤△≤21.59% and -0.70%≤△≤60.28%, respectively. Among pharmacokinetic parameters, AUC met the criteria of KFDA for bioequivalence, while T_(max) and C_(max) didn't meet exactly the criteria of KFDA. But lansoprazole is medicated for long term, and C_(max) did't meet exactly the criteria of KFDA. But lansoprazole is medicated for long term, and absorption amount is more important rather than absorption rate. So considering on clinical aspects of lansoprzole, it was concluded that test capsule, Lansid^(R), is bioequivalent to reference, Lanston^(R) capsule by KFDA.

Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

Kyu-won Hwang,우옥희,Hwan Seok Yong,신봉경,심재정,강은영 대한영상의학회 2008 Korean Journal of Radiology Vol.9 No.2

Lansoprazole is an acid proton-pump inhibiting drug that is used for the treatment of duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease or Zollinger-Ellison syndrome. Although lansoprazole is well known for its gastrointestinal and dermatologic adverse effects, mild pulmonary symptoms are also known to develop from taking this drug. There have been no reports about lansoprazole-induced interstitial lung disease. We report here a case of lansoprazole-induced interstitial lung disease that developed in a 66-year-old man.

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

( Jeong Hoon Lee ),( Hwoon Yong Jung ),( Kee Don Choi ),( Ho June Song ),( Gin Hyug Lee ),( Jin Ho Kim ) 대한소화기기능성질환·운동학회 2010 Gut and Liver Vol.4 No.2

Background/Aims: The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole- and rabeprazole-based triple therapies. Methods: A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C13-urea breath test. Results: Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795). Conclusions: The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms. (Gut Liver 2010;4:201-206)

알긴산 나트륨에 포접된 란소프라졸 장용성 경질캡슐의 특성분석

백종선(Jong Seon Baek),김진수(Jin Su Kim),김원경(Won Kyung Kim),김다윗(David Kim),송정은(Jeong Eun Song),강길선(Gilson Khang) 한국고분자학회 2019 폴리머 Vol.43 No.3

소화성 궤양 및 역류성 식도염을 치료하는 효과적인 약물 치료제로는 양성자펌프 억제제(proton pump inhibitor, PPI)가 있다. 란소프라졸은 PPI계열 약물로 복용 후 낮은 pH에 노출되면 용출률이 저해되어 재석출이 일어난다. 따라서 본 연구에서는 란소프라졸의 약물방출을 제어하기 위하여, 알긴산 나트륨과 습식과립 공정을 이용한 장용성 용질캡슐을 제조하였다. 이 제형은 위액의 산성조건에서 방출이 억제되고, 장액의 중성이나 약 알칼리 조건에서 급속한 약물방출이 일어나는 것을 목표로 하였다. 제조된 경질캡슐의 특성분석을 위해 DSC, XRD, FTIR, SEM을 실행하였다. 이 후 제형이 제대로 설계되었는지 확인하기 위하여 생체 외 용출거동을 통해 변화된 용출률을 확인하였다. 이러한 결과를 토대로 알긴산나트륨이 포접된 란소프라졸 장용성 캡슐은 소화성 궤양 및 역류성 식도염 치료제로 사용 가능함을 확인할 수 있다. An effective drug treatment for peptic ulcer and reflux esophagitis is the proton pump inhibitor (PPI) such as lansoprazole. However when the lansoprazole is exposed to low pH, its dissolution rate becomes low and thus re-precipitation occurs. Therefore an enteric solute capsule was prepared using sodium alginate and wet granulation process. This formulation aimed to inhibit release in acidic conditions of stomach fluid and to cause rapid drug release under conditions of intense, neutral or weakly alkaline conditions. DSC, XRD, FTIR, and SEM were performed to characterize the manufactured hard capsules. In order to confirm that the formulation was properly designed, the dissolution rate was confirmed through in vitro dissolution behavior. Based on these results, it can be confirmed that lansoprazole enteric capsules containing sodium alginate can be used as a treatment for peptic ulcer and reflux esophagitis.

우리나라 프로톤펌프저해제 사용 양상에 대한 연구 : 2016-2020 보건의료빅데이터개방시스템 데이터를 이용한 분석

오주아(Joo-Ah Oh),이규민(Gyu-Min Lee),정서연(Seo-Yeon Chung),조유송(Yu-Song Cho),이혜재(Hye-Jae Lee) 대한약학회 2021 약학회지 Vol.65 No.4

Proton Pump Inhibitors (PPIs) are drugs that inhibit gastric acid secretion and are widely used globally. With the aging population and the rising prevalence of gastrointestinal diseases in Korea, the number of patients using PPIs is increasing. Therefore, we investigated the current state of PPI utilization at the national level using the nationwide database, Healthcare Bigdata Hub compiled by the Health Insurance Review and Assessment Service (HIRA). We extracted the statistics from 2016 to 2020 and re-organized them into monthly utilization by treatments. The cost and volume of use by region, provider type, and diagnostic code were extracted for five PPIs: pantoprazole, rabeprazole, omeprazole, esomeprazole, and lansoprazole. The volume of use was converted into Defined Daily Dose (DDD), which is the standardized unit of utilization. Esomeprazole and rabeprazole were the most commonly used PPIs, and esomeprazole has shown a sharp increase recently. The crude utilization of each region was the highest in Seoul, but that in Daegu and Jeonbuk was the highest after adjusting for the population size. The utilization of PPIs has increased in all diagnostic codes, and Gastroesophageal Reflux Disease (GERD) accounts for the highest proportion. Despite emerging concerns on the adverse outcomes of long-term PPI utilization, their consumption has increased in recent years. These results on the variations by region and trends by diagnostic code thus address a good basis for future research and policies regarding PPIs.

Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro

Liu, K. H.,Kim, M. J.,Shon, J. H.,Moon, Y. S.,Seol, S. Y.,Kang, W,Cha, I. J.,Shin, J. G. Taylor Francis 2005 Xenobiotica Vol.35 No.1

<P>The stereoselectivity of the inhibitory interaction potential of lansoprazole and omeprazole isomers on six human cytochrome P450 forms was evaluated using human liver microsomes. Lansoprazole enantiomers showed stereoselective inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, CYP2C19-catalysed S -mephenytoin 4′-hydroxylation, CYP2D6-catalysed dextromethorphan O -demethylation, CYP2E1-catalysed chlorzoxazone 6-hydroxylation and CYP3A4-catalysed midazolam 1-hydroxylation, whereas omeprazole only inhibited CYP2C19 stereoselectively. Of the P450 forms tested, CYP2C19-catalysed S -mephenytoin 4′-hydroxylation was extensively inhibited by both the lansoprazole and omeprazole enantiomers in a competitive and stereoselective manner; the S -enantiomers of both drugs inhibited the hydroxylation more than the R -enantiomers. The estimated K i values determined for CYP2C19-catalysed S -mephenytoin 4′-hydroxylation were 0.6, 6.1, 3.4 and 5.7 µM for S -lansoprazole, R -lansoprazole, S -omeprazole and R -omeprazole, respectively. The results indicate that although both lansoprazole and omeprazole are strong inhibitors of CYP2C19, the inhibition of CYP2C19 by lansoprazole is highly stereoselective, whereas the inhibition by omeprazole is less stereoselective. In addition, S -lansoprazole, the most potent CYP2C19 inhibitor, is not a good CYP2C19-selective inhibitor owing to its inhibition of other P450 forms.</P>

소화성 궤양 환자에 대한Lansoprazole의 치료 효과

정현용,김진희 최신의학사 1997 最新醫學 Vol.40 No.6