• Journal of Pharmaceutical Investigation
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• v.23 no.2
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• pp.81-87
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• 1993

Five crystalline forms of cimetidine, four anhydrous and a monohydrate, have been prepared, and their thermal behavriours have been studied by differential thermal analysis and thermo-gravimetry. The dissolution rates of the five forms were determined in distilled water at $37^{\circ}C$. The results showed a significant difference in the dissolution rate. Polymorphic transformation occurred spontaneously during storage at room condition and was accelerated by applied energy during formulation process-milling.

• Environmental Analysis Health and Toxicology
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• v.6 no.1_2
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• pp.25-38
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• 1991

The immunopotenciating effects of petroleum ether extract, ethanol extract and butanol fraction of panax ginseng on the immunotoxicity of Cimetidine were investigated in ICR mice. Immune responses were evaluated by antibody production, Arthus reaction, delayed type hypersensitivity (DTH), and rosette forming cell (RFC) in mice, sensitized and challenged with sheep red blood cells. To investigate the change of the non-specific immune responses, phagocyte activity and number of leukocytes in peripheral blood were measured also. The results of this study are summarized as followings; 1. Cimetidine treated group as compared with normal group generally decreased HA, 2-MER, RFC, number of circulating leukocytes and phagocyte activity whereas in-creased Arthus reaction and DTH. 2. The panax ginseng petroleum ether extract combined administration group as compared with the control group remarkably increased HA, 2-MER, number of circulating leukocytes and phagocyte activity. 3. The panax ginseng ethanol extract combined administration group as compared with the control group remarkably increased Arthus reaction, DTH, HA, RFC, number of circulating leukocytes and phagocyte activity. 4. The panax ginseng butanol fraction combined administration group as compared with the control group remarkably increased Arthus reaction, HA, 2-MER, RFC, number of circulating leukocytes and phagocyte activity.

• Korean Journal of Clinical Pharmacy
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• v.10 no.1
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• pp.19-24
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• 2000

The effect of cimetidine on the pbarmacokinetic parameters of cyclosporine (intravenous administration) were determined in 6 healthy volunteers (22-48 years old, 48-62 kg) by cross-over design. Cyclosporine and cyclosporine metabolites in whole blood were analysed by fluororescence polarization immunoassay (TDx-FLX). The blood concentrations of cyclosporine After pretreatment with cimetidine (200 mg bid, for 3days) were increased significantly at 8-12 hrs compared to the control (p<0.05). The ratios of blood concentrations of cyclosporine metabolites (M1, M17) to parent drug were decreased significantly at 8-12 hrs (p<0.05). Total body clearance (CL) was also decreased significantly (p<0.05), and area under the curve $(AUC,\%)$ was increased but not significant.

• Archives of Reconstructive Microsurgery
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• v.21 no.1
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• pp.61-67
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• 2012

Purpose: The purpose of this study was to investigate the role of mast cells and their product, histamine and leukotriene in ischemia-reperfusion injury. Methods: Forty Sprague-Dawley rats were divided into four groups. (Group I: Control group without ischemia, Group II: Normal saline with ischemia, Group III: Cimetidine with ischemia, Group IV: Zafirlukast with ischemia) Skin flap was elevated and ischemic insult was given by clamping the artery for 12 hours. Before reperfusion, the rats were treated with saline, cimetidine and zafirlukast. Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts were evaluated 24 hours after reperfusion. Results: Flap survival rate in the control group was 92.33%, whereas normal saline group had 37.34% survivals. Cimetidine and zafirlukast treated group showed significantly higher survival rates than normal saline group. The neutrophil and mast cell counts in cimetidine and zafirlukast treated group were significantly decreased than normal saline group. Cimetidine treated group showed higher survival rate and lower cell counts than zafirlukast treated group. Conclusion: The administration of cimetidine and zafirlukast can decrease neutrophils and mast cells caused by ischemia-reperfusion and increase flap survivals. It is suggests that antihistamine and leukotriene receptor antagonist have protective effect against ischemia-reperfusion injury to skin flap in rat.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.339-342
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• 2012

Inter-individual pharmacokinetic variation of H2-receptor antagonist is related to genetic polymorphism of CYP2C19. We investigated the frequency of CYP2C19 genetic polymorphism and the treatment duration of cimetidine by CYP2C19 genotypes in functional dyspeptic patients without definite causes who were treated with cimetidine in Korea. One hundred subjects with functional dyspepsia participated in this study from March 1, 2010 to June 30, 2011. They were tested by upper gastrointestinal endoscopy and treated for their dyspepsia with cimetidine. The single nucleotide polymorphisms (SNPs) of CYP2C19 were genotyped using the Seeplex CYP2C19 ACE Genotyping system. There were no significant differences in the demographic, clinical, or laboratory findings among the CYP2C19 subgroups which are wild type homozygote (W/W), heterozygote (W/V), and variant homozygote (V/V). The frequencies of CYP2C19 subgroups were 33 (33%) in W/W, 49 (49%) in W/V, and 18 (18%) in V/V, respectively. The mean duration of cimetidine treatment (in weeks) was the shortest in the V/V among the CYP2C19 genotypes (W/W: $5.1{\pm}1.5$, W/V: $4.0{\pm}1.7$, V/V: $2.1{\pm}0.7$; p<0.001). This study can also act as a basis for further investigation to identify the underlying genetic, epigenetic, or environmental factors in CYP2C19 enzyme activity.

• Journal of the Korean Chemical Society
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• v.55 no.1
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• pp.46-49
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• 2011

A highly sensitive and selective extraction-spectrophotometric method has been developed for determination of trace amounts of cimetidine. This method is based on the extraction of cimetidine as an ion pair with bromothymol blue (BTB) into chloroform and measuring its absorbance at 417 nm. The effect of different variables such as pH, concentration of BTB, volume of chloroform and shaking time was investigated. The effect of interfering ions on the extraction was also studied. The calibration curve was linear in the range of 0.25-8 ${\mu}gmL^{-1}$ with correlation coefficient of 0.9997. The detection limit based on 3Sb was 0.14 ${\mu}gmL^{-1}$ and relative standard deviation for 10 replicated measurements of 1.0 and 4.0 ${\mu}gmL^{-1}$ of cimetidine was 3.2 and 1.49%, respectively. The proposed method was applied to the determination of cimetidine in pharmaceutical samples with good recoveries.

• The Korean Journal of Nuclear Medicine
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• v.23 no.1
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• pp.41-48
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• 1989

$^{99m}Tc-Pertechnetate\;(TcO_4^-)$ is concentrated by the stomach after intravenous injection, allowing the detection of ectopic gastric mucosa. It has been used to develop a noninvasive test of gastric secretion. However the cellular site of concentration is still controversial, that is whether mucin-secreting epithelial cell or acid-secreting parietal cell. This study is planned to investigate the effects of cimetidine and gastric acidity on the retention of $TcO_4^-$ in the gastric wall of the rat. Also we further attempted to clarify the uptake and secreting cell of $TcO_4^-$ in the gastric mucosa. One hundred rats were divided into two groups, preliminary (40 rats) and main examination group (60 rats). Preliminary examination group was composed of fasting group (20 rats) for the detection of the time for reaching stable $TcO_4^-$ retention ratio in gastric wall and post-prandial group (20 rats) for the detection of the time for reaching the maximal gastric acidity. Main examination group was composed of fasting group (30 rats), which was subdivided into control group (10 rats), cimetidine group (10rats), $Mylanta^{(R)}$ group (10 rats) and post?prandial group (30 rats), which was subaivided into 90 min group (10 rats), 90 min cimetidine group (10 rats), and 120 min group (10 rats). Retention ratio (%) of $TcO_4$ in the gastric wall and the pH of the gastric contents were measured in the extracted stomach of the six groups. Gastric wall retention ratio of $TcO_4^-$ was calculated by the gastric wall radioactivity (cpm) divided by total gastric radioactivity (cpm) at 30 mins after intravenous injection of 0.4 mCi of $TcO_4^-$. The results were as follows: 1) The time required for reaching stable $TcO_4$ retention ratio and the lowest gastric PH were 30 min and 90 min, respectively. 2) In the fasting group, the gastric wall retention ratio of $TcO_4^-$ was significantly increased in the cimetidine group, compared with the control group (P < 0.01). However there was no significant difference between the control and $Mylanta^{(R)}$ group 3) The $TcO_4^-$ retention ratios of 90 min and 120 min groups were lower than that of the fasting control group (p < 0.05), either. After administration of cimetidine, the retention ratio was significantly increased in 90 min group (p < 0.01). 4) While $TcO_4^-$ retention ratio and gastric pH were well correlated in the post-prandial 120 min group (r=0.7112, p<0.05), in the post-prandial 90 min and 90 min cimetidine groups correlated poorly. However, there was no correlation in the three fasting groups at all. Referring the above results, we infer that $TcO_4^-$ is secreted into the gastric lumen by both parietal and non-parietal cells, with dominant non-parietal $TcO_4^-$ secretion in the fasting state and dominant parietal $TcO_4^-$ secretion in the stimulated state.

• Journal of Pharmaceutical Investigation
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• v.21 no.4
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• pp.247-251
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• 1991

Effects of aluminum magnesium hydroxide (A) and cimetidine (C) on the pharmacokinetics of minocycline (M) were investigated in female rats. Blood samples were collected at various time intervals until 36 hrs following oral dosing of drugs. Plasma minocycline concentrations were determined by HPLC. Control group (M), $T_1$ group (M+A), $T_2$ group (A+M after 2 hrs), $T_3$ group (M+A after 2 hrs), $T_4$ group (M+C) and $T_5$ group (C+M after 2 hrs) were divided to examine interaction of the drugs with minocycline. Plasma minocyline level-time curves were well described by two-compartment open model with first-order absorption in rats. Antacid treatment was associated with reduced of 71.0, 45.9, 35.7% in minocycline absorption rate $constant(K_{\alpha})$, maximum plasma $concentration(C_{max})$, and relative $bioavailability(F_{rel})$, respectively. Cimetidine treatment group exhibited no significant changes in plasma level-time curve when compared with control group and did not affect minocycline absorption as by any of these three parameters.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.125-131
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• 1992

The effects of domperidone, scopolamine butylbromide and cimetidine on the absorption and bioavailability of ciprofloxacin were studied in female rats. Ciprofloxacin was given in a single oral dose of 30 mg/kg to control group. Ciprofloxacin was concurrently administered with domperidone $(T_1\;group)$, scopolamine butylbromide $(T_2\;group)$, and cimetidine $(T_3\;group)$ to rats, respectively. Significantly changed pharmacokinetic parameters observed in $T_2$group when compared with control group were first-order absorption rate constant, $Ka(4.43{\pm}0.85$\;versus\;2.86{\pm}0.41\;hr^{-1},\;p<0.05)$, time needed to reach peak concentration, $T_{max}\;(32.27{\pm}2.46\;versus\;51.75{\pm}5.51\;min,\;p<0.05)$, area under the plasma concentration-time curve, AUC $(332{\pm}19\;versus\;477{\pm}27\;{\mu}g{\cdot}min/ml,\;p<0.05)$ and absolute bioavailability, Fabs $(60.6{\pm}3.6\;versus\;87.0{\pm}5.0%,\;p<0.05)$. On the other hand, domperidone and cimetidine did not significantly affect the absorption of ciprofloxacin. It is suggested that when scopolamine butylbromide is selected for clinical use, there is need for awareness of the reduction in absorption rate and the enhancement in absorption extent of ciprofloxacin.

• Environmental Analysis Health and Toxicology
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• v.9 no.1_2
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• pp.9-17
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• 1994

The Ha-antagonist, cimetidine, has been shown to retard the hepatic elimination of low and high clearance drugs, and this has been attributed to inhibition of microsomal cytochrome P-450. This study was done to determine the effects of low (50$\mu\textrm{g}$) and high (1mg) dose of famotidine, another histamine H$_2$-receptor antagonist, on hepatic elimination of propranolol compared with cimetidine in the isolated perfused rat liver. Both low and high dose of cimetidine not only inhibited the elimination of propranolol but also increased the area under the perfusate propranolol concentration time curve (AUC). In contrast, low and high dose of famotidine did not affect hepatic elimination of propranolol. Our findings suggest that famotidine has not a propensity for hepatic microsomal inhibition.