• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.367-372
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• 2010

Rabeprazole sodium (RPN) is known to be very unstable at acidic condition or some acidic pharmaceutical excipients such as acrylic acid polymer (carbomer 934) with carboxylic acids. Thus, degradation mechanism of binary blends of rabeprazole with pharmaceutical excipients in a solid state without using solvents at three different ratios (3:1, 1:1 and 1:3) was investigated using Fourier transform infrad (FTIR) spectroscopy. Alkalizer (MgO), neutral hydroxypropymethylcellulose (HPMC 4000) were also tested for comparison. The binary blends were stored under accelerated conditions ($40^{\circ}C$/75% relative humidity) for two weeks. The concentration of thioether rabeprazole from the binary blends with acidic carbomer 934 increased as the rabeprazole concentration decreased. In addition, the degradation half-life of rabeprazole as well as the relative peak area ratios obtained from FTIR spectra of S=O stretching at $1094.1\;cm^{-1}$ decreased consistently as the fraction of carbomer 934 increased due to its sensitivity between the basic benzimidazole nitrogen and carboxylic acid group of carbomer 934. The physical appearance also turned into strong brown color in the presence of carbomer 934. In contrast, there were no significant changes in the degradation kinetics of rabeprazole with MgO and HPMC 4000 in a solid state. This present study demonstrated that the solid-state compatibility test with the aid of HPLC chromatographic and FTIR spectral analyses could offer a valuable methodology to select suitable pharmaceutical excipients and to elucidate the degradation mechanism of RPN for drug formulations at the early formulation stages.

• 분석과학
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• 제32권5호
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• pp.185-195
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• 2019

Over the past decades, chiral switch of the proton pump inhibitors (PPIs) has been received widespread attention in therapeutic advantages as well as pharmaceutical analysis. In present study, the influence of cyclodextrins (CDs) on the chiral separation of four common PPIs (lansoprazole, omeprazole, pantoprazole, and rabeprazole) was investigated. The results demonstrated that capillary electrophoresis (CE) with dual CDs as a chiral selector system is a possible and promising method for the enantioseparation of these PPIs. Rabeprazole, which is the most challenging and acid-labile candidate among four PPIs, was selected for further development of the technique. To optimize CE condition, the effects of capillary parameters and background electrolytes on the enantioseparation were investigated. Finally, the best chiral separation was acheived by using sulfobutyl ether-${\beta}$-CD, and ${\gamma}$-CD as dual chiral selectors. The developed CE method not only provided the effective chiral separation but also showed the good stability of rabeprazole. The proposed method was successfully validated according to the International Conference on Harmonization guideline and effectively applied to determine rabeprazole enantiomers in commercial rabeprazole tablets, with recoveries ranging from 97.17 % to 103.29 % of the label content.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.73-78
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• 2009

A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

• 대한기관식도과학회지
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• 제10권2호
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• pp.35-42
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• 2004

Background and objective : Rabeprazole is a new generation proton pump inhibitor, which has a rapid onset after first dose, predictable efficacy in all patients regardless of CYP2C19 genotype status, and less nocturnal acid breakthrough. The aim of the study is to investigate clinical efficacy and safety of rabeprazole sodium (Pariet 10mg qd)when administered once daily to patients with laryngopharyngeal reflux(LPR) disease. Methods : Among the patients who had visited the Department of Otolaryngology, those with LPR symptoms, had undergone laryngoscopy. Symptoms and endoscopic laryngeal sings were recorded initially, at 1 month, 2 months, 3 months, and more than 3 months, All patients were evaluated for clinical efficacy on the basis of symptom scores, reflux finding score(RFS), and side effects. Results : In general, most symptom scores and RFS improved over the time. Efficacy of the Pariet on LPR-related symptoms were $63.2\%,\;77.5\%,\;78.7\%,\;and\;90.9\%$ before 4 weeks, 4 to 8 weeks, 8 to 12 weeks, and after 12 weeks respectively. Efficacy on the RFS were $61.8\%,\;78.4\%,\;82.9\%,\;and\;85.5\%$ before 4 weeks, 4 to 8 weeks, 8 to 12 weeks, and after 12 weeks respectively. Pariet was well tolerated and was associated with few drug-related side effects. Conclusion Because of its efficacy and safety, Pariet may prove to be an alternative to currently available proton pump inhibitors.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 2005년도 제57차 추계 학술대회 연제집
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• pp.463-463
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• 2005

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 2004년도 추계학술대회 초록집
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• pp.24-24
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• 2004

• 대한기관식도과학회지
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• 제9권1호
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• pp.60-66
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• 2003

Although there is a wide range of diseases caused by gastric acid reflux and the number of cases is on the rise, it is difficult for the laryngologist to make the correct diagnosis. The treatment for laryngopharyngeal reflux can be grouped into 3 categories - changes in lifestyle, medication, and surgery. The medication used to treat laryngopharyngeal reflux are prokinetic agents and acid supressive agents such as antacids, H2 blockers, and PPIs(Proton pump inhibitor). Rabeprazole sodium($Pariet^{\circledR}$) is a newly developed agent belonging to the PPI group, but in contrast with the existing drugs such as omeprazole, lansoprazole, pantoprazole, has a low dependency on CYP2C19 during the metabolic cycle. Thus, it is known to have a quick but fixed antiacid effect and less individual differences. We analyzed 2166 patients from 32 hospitals who were prescribed $Pariet^{\circledR}$ from May, 2001 to April, 2002. The patients were divided into 4 groups according to the duration of treatment - Group 1: 1-14 days, Group 2: 15-28 days, group 3: 29-56 days, Group 4: more than 56 days. The cases were then analyzed for improvement of 8 symptoms(heart bum, regurgitation, chronic cough, hoarseness, globus sensation, chronic throat clearing, sore throat, and dysphagia), improvement on laryngoscope, usefulness to the doctor, and complication development. Of the total of 2116 patients, 1627(75.1%) cases showed at least 50% improvement of symptoms and the amount of improvement increased according to the duration of medical treatment. Most of the patients showed objective improvement on the laryngoscope, with 32.9% showing significant improvement and 38.7% showing moderate improvement. 37.6% of the doctors questioned replied that $Pariet^{\circledR}$ was very useful and 50.3% said it was useful, showing that most were satisfied with the treatment results. The complications known to develop after taking PPI are headache, nausea, diarrhea, abdominal pain, constipation, dizziness, fatigue, and of these, only a small percentage of the patients complained of mild headache. $Pariet^{\circledR}$ has shown to be a relatively safe and effective drug for the treatment of laryngopharyngeal reflux.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 2002년도 제2차 추계학술대회
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• pp.9-9
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• 2002

이비인후과 영역에 있어서 위산 역류에 의한 질환의 진단은 쉽지 않고 분명하지 않은 점이 많지만, 병변의 영향은 광범위하며, 실제로 역류에 의한 증상을 가지고 내원하는 환자도 증가하는 추세이다. 인후두역류질환의 치료는 크게 생활습관의 변경, 약물복용, 항역류수술로 나눌 수 있으며, 사용약제는 크게 두 부류로 나누는데, 제산제, H2 수용체 차단제, PPI(Proton Pump Inhibitor) 제제와 같은 산억제 약물군과 Prokinetic 약물군이다. Rabeprazole sodium(Pariet(R))은 PPI 제제에 해당하는 약제로 기존의 omeprazole, lansoprazole, pantoprazole과는 달리 대사 과정 중 CYP2C19에 대한 의존도가 낮아, 개체 간 차이가 적고 빠르고 일정하게 산분비 억제 효과를 나타내는 것으로 알려져 있은 약물이다. 2001년 5월부터 2002년 4월까지 32개 병원에서 Pariet(R) 를 복용한 2166명의 환자를 대상으로 분석하였다. 복용기간에 따라 4군(1군;1-14일, 2군;15-28일, 3군;29-56일, 4군:57일 이상)으로 나누었으며, 8가지 증상(Heart burn, Regurgitation, Chronic cough, Hoarseness, Globus sensation, Chronic throat clearing, Sore throat, Dysphagia)에 대한 호전 여부 및 후두내시경상 개선 정도, 의사에 의한 유용도 평가, 부작용 발생 여부에 대해 연구하였다. 증상개선율 50%이상을 치료 반응군으로 했을때 전체 2166명중 1627명(75.1%)에서 증상의 호전을 보았으며, 이는 복용기간이 길수록 증가하였다. 후두 내시경상 개선 정도는 현저한 개선이 32.9%, 중등도 개선이 38.7%로 대부분 환자에서 객관적인 병변의 호전을 보였으며, 유용도 평가에서는 매우 유용이 37.6%, 유용이 50.3%로 치료효과에 대한 만족도도 높은 것을 알수 있었다. PPI 제제의 부작용으로 보고되고 있는 두통, 오심, 설사, 복통. 변비, 어지럼증. 피곤 중. 소수의 환자가 두통을 호소하였으나, 그다지 심각한 정도는 아니었다. 인후두역류증 치료제로서 Pariet(R) 는 비교적 안전하고 효과가 높은 약물임이 임상 연구 결과 밝혀졌기에 보고하는 바이다.

• 대한후두음성언어의학회지
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• 제14권1호
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• pp.26-29
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• 2003

Background and Objectives : Gastric acid reflux has been suggested to have an association with sleep apnea(SA). This study's aim is to evaluate the relationship between reflux laryngitis and SA through the fact that the treatment of reflux laryngitis may impact the snoring and SA related symptoms in selective individuals. Methods : Population consist of 24 males and 10 female aged 34 to 66 years(mean age 50 years) confirmed by Reflux Finding Score(RFS) of PC Belafsky. Thirty four patients with reflux laryngitis and associated symptoms of SA were treated with proton pump inhibitor(Rabeprazole sodium 10mg/day) for 60 days. The degree of snoring and apnea related symptoms were evaluated using questionnaires, and palatine tonsillar hypertropy(PTH) and RFS were compared preoperatively and postoperatively. Results : After antireflux treatment for 60 days, the snoring(p=0.039), daytime sleepiness(p=0.002), and concentration(p=0.011) were significantly improved(p<0.05) and RFS was significantly decreased(p=0.000), but morning headache(p=0.057) and sleep apnea(p=0.083) were not significantly improved(p>0.05) and PTH was not significantly decreased(p=0.328). Conclusion : Treatment of reflux laryngitis significantly impacted the snoring, daytime sleepiness, and concentration in selective individuals. These results suggest some close relationship between reflux laryngitis and SA, and the treatment of reflux laryngitis may be some effective in those with both disorders.