• Journal of Pharmaceutical Investigation
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• 제10권3호
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• pp.33-45
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• 1980

In order to increase the solubility of metoclopramide, various ratio coprecipitates with polyvinylpyrrolidone (M.W. 40,000) were prepared. The experiments of the solubility, physicochemical characteristics were quantitatively developed. The solubility increased as the ratio of rnetoclopramide to polyvinylpyrrolidone in metoclopramide-polyvinylpyrrolindone coprecipitate increased. In powder state, the dissolution rate of metoclopramide-polyvinylpyrrolidone coprecipitate was greater than that of metoclopramide and metoclopramide-polyvinylpyrrolidone physical mixture. Dissolution characteristics of non-disintegrating disk with constant surfacearea was in accord with Noyes-Nernst equation. The intrinsic dissolution rate, G, at $37^{\circ}C$ was $3.98{\times}10^{-7}M/cm^2{\cdot}min$ for metoclopramide, $2.26{\times}10^{-6}\;M/cm^2{\cdot}min$ for 1 : 5 metoclopramide-polyvinylpyrrolidone coprecipitate, respectively. Accordingly, activation energy of metoclopramide was 15,061cal/M, 9,178cal/M for 1 : 5 metoclopramide-polyvinylpyrrolidone coprecipitate and the activation energy decreased as the coprecipitate was formed. X-ray diffraction study revealed the fact that metoclopramide was crystalline, in contrast, there was no crystallinity evident in the 1 : 5 metoclopramide-polyvinylpyrrolidone coprecipitate. There was no difference between physical mixture and coprecipitate in TLC, UV and NMR studies. From the comparision between physical mixture and coprecipitate in IR spectrum, the interaction such as association between metoclopramide and polyvinylpyrrolidone was considered. But the association was easily dissociated in methanol solution.

• Journal of Pharmaceutical Investigation
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• 제9권2호
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• pp.11-21
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• 1979

It has been reported from our department that a few agents, such as $K_2S_2O_5,\;NaHSO_3,$ nicotinamide have a marked stabilizing effect in vitro on metoclopramide which is relatively unstable compound. In order to study the effect of these stabilizers on the action of metoclopramide in vitro, the fate of this compound combined with $K_2S_2O_5,\;NaHSO_3$ and nicotinamide, respectively, was studied and furthermore, the change of the biological activity of metoclopramide due to these stabilizers was studied by using the isolated stomach strip of rat. The blood concentration of metoclopramide was measured by using Bakke's method at the various time after intravenous injection of the mixed metoclopramide solution with the stabilizers. In order to study the excretion of the drug, rabbits were anesthesized and catheterized into bladder for withdrawal of urine. After intravenous injection of the mixed metoclopramide solution, urine was collected for 5 hours and the conjugated forms of metoclopramide as well as the free form were determined by using Arita's method. In the biological study of the metoclopramide combined with stabilizers, the contractability of the isolated rat stomach strip was observed by using polygraph recorder. The results were following: 1. When metoclopramide was administered with nicotinamide as stabilizer, the blood concentration of the unchanged from and the rate of the clearance of this compound were very similar to that of metoclopramide alone. On the other hand, other stabilizers, $K_2S_2O_5\;and\;NaHSO_3$, brought about 40% decrease in blood concentration of the unchanged form at 15 min after intravenous injection however, the rate of clearance of metoclopramide with $K_2S_2O_5\;or\;NaHSO_3$ was very slow. 2. In the case of urinary excretion, the excretory pattern of the metabolites of metoclopramide with $NaHSO_3$ or nicotinamide was very similar to that of metoclopramide alone. But metodopramide plus $K_2S_2O_5$ group showed the maked depression of excretion for first 1 hour. 3. In composition of metabolites, when metoclopramide was administered with $K_2S_2O_5$ or $NaHSO_3$, the sulfonate conjugation was predominant. But the glucuronic acid conjugation was predominant in metoclopramide plus nicotinamide gronp. 4. In the experiments on the biological activity of the metoclopramide, this compound exhibited the marked contracting effect in isolatd rat stomach strip. Specially, the meetoclopramide combined with $K_2S_2O_5$ showed the strong contraction of the isolated strip, suggesting the potenciating effect of $K_2S_2O_5$ on the action of metoclopramide in the isolated strip.

• Journal of Pharmaceutical Investigation
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• 제14권1호
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• pp.11-18
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• 1984

This paper was attempted to study on the effect of metoclopramide or propantheline on the absorption rate and bioavailability and pharmacokinetic parameter of fluorouracil in rats and rabbits. The result are as follows; Metoclopramide increased the absorption rate of fluorouracil but propantheline decreased in situ experiment with rat small intestine. Metoclopramide increased the blood level and relative bioavailability and absorption rate constant of fluorouracil in rabbits. Prolonged the peak blood level (tmax) and decreased the absorption rate constant (Ka) but did not affect the blood level and relative bioavailability of fluorouracil in rabbits. As a matter of fact, it is considerd that the coadministration of metoclopramide or propantheline is more desirable than the single administration of fluorouracil for available dosage regimen.

• The Korean Journal of Pain
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• 제10권2호
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• pp.203-207
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• 1997

Background: To date, there are no controlled studies assessing the effect of metoclopramide administered epidurally to prevent nausea and vomiting associated with epidural morphine for postoperative analgesia. This study was undertaken to determine the effectiveness of continuous epidural infusion of metoclopramide, combined with epidural morphine, in reducing nausea or vomiting associated with epidural morphine and minimizing the side effects of metoclopramide. Methods: Sixty patients undergoing elective gynecologic surgery were randomly assigned to one of two study groups. Patients received continuous epidural morphine infusion (6.0 mg/day) following a bolus loading dose of 3.0 mg (Group A), or epidural mixture of morphine (6.0 mg/day) plus metoclopramide (20 mg/day) following a bolus loading dose (morphine 3.0 mg, metoclopramide 10 mg)(Group B). For the first 24 postoperative hours, incidence of nausea or vomiting, need for antiemetic therapy, level of sedation, degree of pain and pruritus, and adverse effects associated with metoclopramide were evaluated. Result: Incidence of nausea or vomiting and number of patients who required antiemetic therapy were significantly less in Group B, than in Group A (P<0.05). There were no significant differences between groups with regard to adverse effects associated with metoclopramide such as sedation, extrapyramidal reaction and other side effects (P=NS). Conclusion: We conclude simultaneous titration of morphine and metoclopramide via epidural continuous infusion following epidural bolus injection of the mixture reduces nausea or vomiting associated with epidural morphine while preventing side effects of metoclopramide.

• The Korean Journal of Pain
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• 제11권1호
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• pp.86-90
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• 1998

Background: There are no controlled studies assessing the effect of metoclopramide and droperidol administered epidurally for the prevention of nausea and vomiting associated with epidural morphine. This study was undertaken to compare the effectiveness of continuous epidural metoclopramide and droperidol in reducing nausea and vomiting associated with epidural morphine. Methods: Ninty patients undergoing elective gynecologic surgery were randomly assigned to one of three study groups; Group A(n=30) patients received continuous infusion of epidural morphine(6.0 mg/day) following a bolus loading dose of 3.0 mg; Group B(n=30), epidural mixture of morphine and droperidol(5.0 mg/day) following a bolus loading dose(morphine 3.0 mg, droperidol 1.5 mg); Group C, (n=30), epidural mixture of morphine and metoclopramide(20 mg/day) following a bolus loading dose(morphine 3.0 mg, metoclopramide 10 mg). For the 24 postoperative hours, the incidence of nausea and vomiting, degree of pain, level of sedation and other adverse effects were evaluated. Results: Incidence of nausea and vomiting, and number of patients who required antiemetic therapy were significantly less in Group B and C than in Group A(P<0.05). Patients in Group A and C were less sedated than those in Group B. Conclusions: We conclude metoclopramide is more effective than droperidol for postoperative nausea and vomiting due to its lower of sedative effect.

• 한국임상약학회지
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• 제33권2호
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• pp.122-127
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• 2023

Background: This study was aimed to identify the safety signals of metoclopramide in Korea Adverse Event Reporting System (KAERS) database by proportionality analysis methods. Methods: The study was conducted using Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) reported from January 2013 to December 2017 through KAERS. Signals of metoclopramide that satisfied the data-mining indices of proportional reporting ratio (PRR), reporting odds ratio (ROR) and information component (IC) were defined. The detected signals were checked whether they included in drug labels in the Ministry of Food and Drug Safety (MFDS), U.S. Food and Drug Administration (FDA) and Micromedex^®. Results: A total number of drug AE reports associated with all drugs of data in this study was 2,665,429. Among them, the number of AE reports associated with metoclopramide was 22,583. Forty-two meaningful signals of metoclopramide were detected that satisfied with the criteria of data-mining indicies. Especially neurological signals including extrapyramidal reactions, represented in the safety letter of regulatory agencies were identified in this study. Conclusion: Neurological signals of metoclopramide including extrapyramidal reactions were detected. It is believed that this search for signals can contribute to ensuring safety in the use of metoclopramide.

• 약학회지
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• 제22권1호
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• pp.27-32
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• 1978

Metoclopramide reacts with ammonium cobaltothiocyanate to form a stable ion pair which has an absorption maximum of 625mm. The reaction product was insoluble in water but soluble in most organic solvents. 1,2-Dichlorethane was the best extracting solvent among the several organic solvents tested. Metoclopramide can be determinded not only by visible light spectrophotometry but also indirectly by estimation of cobalt in the organic phase by flameless atomic absorption spectrophotometry. Linear relationship was found between absorbance and concentration in the range of 10$^{-4/}$-10$^{-3}$M by spectrophotometry and 10$^{-5}$-10$^{-4}$M by flameless atomic absorption spectrophotometry. The coefficient of variation by spectrophotometry was 0.9% and that of flameless atomic absorption was 1.8%. There was no interference with excipients, pH, temperature and reaction time. With this method, it is possible to determine accurately metoclopramide and tertiary amines in pharmaceutical preparations.

• 대한약리학회지
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• 제25권1호
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• pp.31-42
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• 1989

Metoclopramide (MCP)는 역류성식도염, 위하수증, 항암제에 의한 구토 증상을 치료하는데 사용되고 있는 dopamine수용체 차단제로 알려져 있다. 본 연구에서는 흰쥐의 적출 관류부신에서 catecholamine (CA)의 분비작용에 미치는 영향을 검토하여 다음과 같은 결과를 얻었다. MCP는 부신정맥내로 주입하였을때 용량의존적으로 CA 분비작용을 나타냈다. 이러한 MCP의 CA 분비작용은 atropine 전처치로 차단되었으나 chlorisondamine 처치에 의해서는 완전 차단되지 못하였다. MCP 분비작용은 physostigmine, adenosine, ouabain의 전처치로 현저히 증강되었다. 그러나 5mM-EGTA 함유 $Ca^{++}-free\;Krebs$ 액으로 관류하였을때 MCP의 CA 분비작용은 현저히 억제되었다. MCP (200 ug/30 min)를 관류한 실험에서는 KCI이나 acetylcholine의 CA 분비작용이 유의있게 감소되었다. 이상의 실험결과로 보아 MCP는 칼슘의존적기전에 의해 CA를 유리 시키며, 이러한 분비작용은 부신에서 nicotine수용체 보다도 muscarine수용체의 활성화에 더 기인 되는 것으로 생각되며, chromaffin cell에 대한 일분 직접작용도 개재되어 나타나는 것으로 사료된다.

• 대한핵의학회지
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• 제12권2호
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• pp.7-16
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• 1978

To elucidate the depaminergic control of T.S.H. secretion, we analized the pattern of T.S.H. secretion in seven normal controls and nine primary hypothyroid subjects, before and after single or combined administration of specific dopaminergic,receptor blocker, metoclopramide, and specific depaminergic receptor stimulant, bromergocryptine(CB-154). The results obtained were as follows: 1) There was a significant rise in T.S.H. levels after intra venous injection of metocloramide (10mg) in hypothyroid subjects. But there was no significant rise in T.S.H. levels in normal controls. The T.S.H. response to metoclopramide varied considerably, being large in mild cases and small in severely hypothyroid subjects. 2) There was a significant fall in T.S.H. levels after oral administration of bromergocryptine (2mg) in hypothyroid subjects, but there was no significant fall in T.S.H. levels in normal controls. 3) There was no significant fluctuation in T.S.H. levels after combined administration of both metoclopramide and bromergocrytine. 4) There was no significant fluctuation in T.S.H. levels after intravenous injection of normal saline(2ml) in both hypothyroid and normal subjects. 5) There was no significant change in serum $T_3\;and\;T_4$ after administration of metoclopramide and and bromergocryptine respectively and serially. These data support the fact that there is a dopaminergic control in the secretion of T.S.H. in the human.

• 대한수의학회지
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• 제45권2호
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• pp.297-302
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• 2005

The present experiment was performed in order to know the anti-emetic effect of acupuncture, aquapuncture with metoclopramide and moxibustion on the xylazine induced emesis in dogs. The animals were devided into a control group (non-acupoint) and two experimental groups (BL-20 and LIV-13), respectively. Acupuncture, aquapuncture with metoclopramide (1 mg/kg) and moxibustion were applied to animals for 20 minutes before xylazine injection (2.2 mg/kg, IM). In acupuncture group, the emetic rates in BL-20 (16.7%) and LIV-13 (16.7%) were lower than that of control group (50%), respectively. In aquapuncture group, the emetic rates in BL-20 (16.7%) and LIV-13 (0.0%) were lower than that of control group (50%), respectively. In moxibustion group, the emetic rates in BL-20 (50%) and LIV-13 (16.7%) were lower than that of control group (83.3%), respectively. Considering above the findings collectively, it is considered that acupuncture, aquapuncture with metoclopramide and moxibustion at BL-20 and LIV-13 are effective and especially aquapuncture with metoclopramide at LIV-13 is the most effective treatment to prevent the emesis induced by xylazine among groups.