• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.9 no.2
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• pp.115-127
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• 1998

Laryngopharyngeal reflux(LPR) is one firm of the gastroesophageal reflux diseases(GERD). It is known to cause various kinds of otolaryngologic symptoms such as hoarseness, foreign body sensation in throat, chronic throat clearing, chronic cough, etc. Disease entities diagnosed by otolaryngologists as posterior laryngitis, globus pharyngeus should be suspected as LPR-related diseases. In this multi-center trial, we tried to evaluate the effect of cisapride(10mg tid) on LPR-related symptoms as the part I study(CIS-KOR-051) in 19 centers, and as the part II study(CIS-KOR-052) comparative evaluation of effect between cisapride(10mg tid) and ranitidine(150mg bid) on LPR-related symptoms in 4 centers. In part I study, efficacy of cisapride on LPR-related symptoms after 4 weeks was 53.5% and that of after 8weeks was 77.9% in per protocol(PPA) analysis group. In part II study, efficacy of the cisapride was much better than that of ranitidine not only from 8 weeks trial(p<0.001) but also from 4 weeks trial(p<0.021) in PPA group. In the multiple logistic regression analysis among the parameters which affect the efficacy of the treatment, cisapride prescribed group showed 10 times greater than that of ranitidine prescribed group(p<0.0001, Odds ratio : 10) in PPA group. LPR was proved by 24Hr double probe pHmetry in 13 patients out of 19 patients tested(68.4%). Thus these results indicated that inducing the improvement of motility functions could affect the amelioration of the LPR-related symptoms much better than reducing acid secretion from the stomach. And maybe it suggests that LPR-related symptoms mainly developed by the reduced motility functions of the esophagus and/or delayed gastric emptying.

• Journal of Life Science
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• v.24 no.3
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• pp.260-265
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• 2014

Dried Citrus unshiu peels (Aurantii Nobilis Pericarpium; ANP) are used as a traditional folk medicine for the treatment of gastrointestinal (GI) motility disorders in East Asia, including Korea. In the present study, an ethanolic extract of ANP (ANP-E) exhibited no significant toxicity in mice, even at an oral dose of 5 g/kg. The effects of ANP-E on GI motor function were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal mice and mice with experimental GI motility dysfunction (i.e., peritoneal irritation by acetic acid; PIA). In normal mice, ANP-E significantly increased the ITR in a dose-dependent manner. The ITR in the PIA mice was significantly retarded compared to that in the normal mice. However, ANP-E significantly inhibited this retardation in a dose-dependent manner. Furthermore, in all the models, the potency of ANP-E appeared to be same or higher than that of cisapride, which was used predominantly for the treatment of various GI motility disorders in humans in the 1900s but was removed from the market in 2000 due to fatal side effects. The results suggest that ANP-E has potential as a new prokinetic agent that could be used as a substitute for cisapride.

• Korean Journal of Clinical Pharmacy
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• v.10 no.1
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• pp.25-29
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• 2000

Bioequivalence of cisapride-containing $Cisaplus^{(R)}$ tablets (Daewoong Co.) to reference $Prepulsid^{(R)}$ tablets (Janssen Co.) was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy volunteers were divided randomly into two groups and administered orally at a cisapride dose of 10 mg in a $2\times2$ crossover design. There was a 1-week washout period between the treatments. Blood samples were taken at predetermined time intervals for 48 hr and the plasma cisapride concentrations were determined by an HPLC with UV detector. The area under the plasma drug concentration-time curve (AUC) was caltulated from time zero to the last sampling time by a linear trapezoidal method. The maximum observed plasma drug concentration ($C_{max}$) and the time to $C_{max}\;(T_{max})$ were estimated directly from the drug concentration-time data. Analysis of variance (ANOVA) showed that the apparent differences for AUC, $C_{max}\;and\;T_{max}$ were $-7.52\%,\;-8.91\%\;and\;-15.55\%$, respectively. The minimum detectable differences for AUC, $C_{max}\;and\;T_{max}$ between formulations were $14.52\%,\;11.57\%\;and\;28.00\%$ respectively, at $\alpha=0.05\;and\;1-\beta=0.8\;levels.\;The\;90\%$ confidence intervals for AUC, $C_{max}\;and\;T_{max}\;were\;-16.00\sim0.97\%,\;-15.67\sim-2.15\%\;and\;-31.88\%\sim0.84\%$, respectively. These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cisapride are bioequivalent.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• Journal of Life Science
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• v.29 no.12
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• pp.1345-1350
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• 2019

Our recent study has revealed that in vivo intestinal transit rate (ITR) in normal mice was significantly increased by the administration of an aqueous extract of dried Gentiana scabra rhizomes and roots (GS-W) in a dose-dependent manner. Following on from our previous study, the effect of GS-W on ITR was measured in mice with experimentally induced gastrointestinal motility dysfunctions (GMDs) in the present study. GS-W showed no significant acute toxicity even at an oral dose of 5 g/kg to mice. ITR was significantly retarded in the GMD mice compared with that in normal mice, and this retardation was significantly recovered by the oral administration of GS-W in a dose-dependent manner. Furthermore, the ITR value of GS-W at a dose of 1 g/kg appeared to be higher than that of cisapride, which was predominantly prescribed for human patients with various GMDs in the late 1900s but was withdrawn from the market in 2000 due to its fatal side effects. The current results suggest that GS-W is a potential substitute for cisapride to prevent or alleviate human GMDs.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.55-59
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• 2000

Bioequivalence of two cisapride tablets, test drug ($Cisple^{\circledR}$ tablet: Hanmi Pharm Co., Ltd.) and reference drug ($Prepulsid^{\circledR}$ tablet: Janssen Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty two healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a $2{\times}2$ crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. $AUC_{0-36hr}$ (area under the plasma concentration-time curve from time zero to 36 hr), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 5.38, 6.17 and 0.00% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The powers $(1-\beta)$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ were over 0.9. Minimal detectable differences $(\Delta)$ at ${\alpha}=0.05,\;1-{\beta}=0.8$ were less than 20% (i.e. 17.67, 14.84 and 19.72% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The 90% confidence intervals $(\delta)$ for these parameters were also within ${\pm}20%$ $(i.e.\;-4.97\;{\le}{\delta}{\le}\;15.73,\;-2.53{\le}{\delta}{\le}\;14.86\;and\;-11.55{\le}{\delta}{\le}\;11.55$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.

• Journal of Life Science
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• v.29 no.6
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• pp.735-739
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• 2019

The dried rhizomes and roots of Gentiana scabra (GS) have been frequently prescribed as a traditional folk medicine in East Asia (including China, Japan, and Korea) for the treatment of various pathophy-siological conditions, such as inflammatory skin diseases, anorexia, indigestion, gastric infections, and diabetes mellitus. In the present study, the effects of aqueous (GS-W) and ethanolic (GS-E) extracts of GS on gastrointestinal (GI) motor function were investigated by measuring the in vivo gastric emptying rate (GER) and the intestinal transit rate (ITR) in mice. The GER was significantly increased by GS-W at a dose of 1 g/kg. The ITR was significantly increased by GS-W (at doses of 0.1 and 1 g/kg) or GS-E (at a dose of 1 g/kg) in a dose-dependent manner. Furthermore, the ITR value of GS-W (at a dose of 1 g/kg) appeared to be higher than that of cisapride, which was the most prominent prokinetic agent in the 1900s but was removed from the market in 2000 due to its fatal side effects. The above results suggest that GS-W might be a potential prokinetic agent to replace cisapride.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.217.2-217.2
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• 2000

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.299-306
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• 1992

Gastic emptying scan in diabetic patients is widely used to assess the degree of motility disturbance and the symtoms such as nausea, vomiting, bloating, abdominal pain and early gastric fullness which we can't find anatomic lesion by fiberoscopic or barium study In order to determine the relationship among diabetic gastropathy, neropathy, retinopathy and disease duration, gastric emptying scan using $^{99m}Tc-tin$ colloid labeled scramble egg in hamburger was performed in 10 healty male controls and 50 diabetic patients which were subdivided to no neuropathy, peripheral neuropathy and autonomic neuropathy groups according to the degree of diabetic neuropathy and no retinopathy, background retinopathy and proliferative retinopathy groups according to the degree of diabetic retinopathy. After medication of cisapride for 2 weeks, we observed the presence of improvement of gastric motility in diabetics. The results were as following: 1) In controls, gastric emptying time (GET1/2) was $75{\pm}13.6$ min and 2 hour gastric retension rate (GRR2) was $32{\pm}11.1%$. 2) In diabetics, GET/2 was prolonged more than 2 hours and GRR2 was $58{\pm}23.1%$. According to degree of neuropathy, GET1/2 was prolonged more than 2 hours in all three groups and GRR2 was $54{\pm}24.1%$ in no neuropathy group, $57{\pm}24.3%$ in peripheral neuropathy group and $69{\pm}24.6%$ in autonomic neuropathy group. According to degree of retinopathy, GET1/2 was $110{\pm}23.4$ min in no retinopathy group and prolonged more than 2 hours in other two groups and GRR2 was $45{\pm}21.6%$ in no retinopathy group, $71{\pm}19.7%$ in background retinopathy group and $73{\pm}21.5%$ in proliferative retinopathy group. 3) After cisapride medication for 2 weeks, GET1/2 and GRR2 were improved as $90{\pm}14.6$ min and $40{\pm}13.8%$ (initial GET1/2 and GRR2 were above 2 hours and $61{\pm}15.4%$). We can conclude from above findings that gastropathy in diabetic neuropathy suggesting main underlying factor in motility disorder The degree of retinopathy and disease duration were correlated with severity of gastropathy in diabetics. From the results of gastric emptying scan, we can conclude that cisapride was useful drug for improving diabetic gastropathy and gastric emptying scan was valuable for assessing severity of diabetic gastropathy as non-invasive method.

• 대한핵의학회:학술대회논문집
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• 1992.06a
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• pp.201.1-201.1
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• 1992