Oral Administration Of Cimetidine Research Articles

Creatinine clearance after cimetidine administration in a new short procedure: comparison with plasma and renal clearances of iohexol.

BackgroundCreatinine clearance after cimetidine administration (Cim-CreatClr) was once proposed as a method of glomerular filtration rate (GFR) measurement, but has been largely abandoned. We investigated whether a new short procedure for Cim-CreatClr determination could be considered an appropriate method for GFR measurement.MethodsA 150-min protocol involving oral cimetidine administration was developed to determine Cim-CreatClr. In total, 168 patients underwent simultaneous assessments of creatinine clearance before and after cimetidine administration [basal creatinine clearance (Basal-CreatClr) and Cim-CreatClr, respectively], renal iohexol clearance and plasma iohexol clearance (R-iohexClr and P-iohexClr, respectively). We compared the agreement between the various methods of GFR measurement, using Bland–Altman plots to determine biases, precisions (standard deviation of the biases) and accuracy (proportions of GFR values falling within 10, 15 and 30% of the mean: P10, P15 and P30, respectively).ResultsAfter cimetidine administration, Basal-CreatClr decreased by 19.8% [95% reference limits of agreement (95% LoA): −2.2 to 41.7%]. The bias between Cim-CreatClr and P-iohexClr was −0.6% (95% LoA −26.8 to 28%); the precision was 14.0%; P10, P15 and P30 were 57.1% [95% confidence interval (95% CI) 49.3 to 64.7%], 73.2% (95% CI 65.8 to 79.7%) and 97.0% (95% CI 93.2 to 99.0%), respectively. Due to the positive bias (16.7%; 95% LoA −3.6 to 36.9%) of Cim-CreatClr relative to R-iohexClr, accuracy of Cim-CreatClr relative to R-iohexClr was poor despite a good precision (10.3%).ConclusionsOur study shows a high level of agreement between Cim-CreatClr and P-iohexClr. These results suggest that this short Cim-CreatClr procedure is a valid method for GFR measurement, which might be useful, in particular, in situations in which P-iohexClr is not suitable or not available.

Gastroprotective and Ulcer Healing Effects of Camel Milk and Urine in HCl/EtOH, Non-steroidal Anti-inflammatory Drugs (Indomethacin), and Water-Restraint Stress-induced Ulcer in Rats.

Background:Camel milk has been reportedly used to treat dropsy, jaundice, tuberculosis, and diabetes while camel urine is used to treat diarrhea and cancer. However, there is no scientific evidence on the antiulcer activity of camel milk and urine. Thus, the present is designed to investigate the gastroprotective and ulcer healing effect of camel milk and urine on experimentally induced gastric ulcer models in rats.Materials and Methods:The gastroprotective effect was investigated in HCl/EtOH, water-restraint stress (WRS) and non-steroidal anti-inflammatory drugs (indomethacin)-induced ulcer models while ulcer healing activity was investigated in indomethacin-induced ulcer model. Cimetidine (100 mg/kg) was used as a standard antiulcer drug.Results:Acute toxicity study done up to a dosage of 10 ml/kg of camel milk and urine showed no signs of toxicity and mortality among the rats, indicating the present dosage of 5 ml/kg is safe to be administered to the rats. In the HCl/EtOH model, oral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk (5 ml/kg) significantly (P < 0.05) inhibited gastric lesions by 83.7, 60.5 and 100%, respectively. In the WRS-induced model, cimetidine, and camel urine showed an ulcer inhibition of 100% while camel milk showed an inhibition of 50%. Similarly, in the indomethacin-induced ulcer model, cimetidine, camel milk, and urine showed an ulcer inhibition of 100, 33.3, and 66.7%, respectively. In addition, camel milk and urine also showed a significant (P < 0.05) ulcer healing effect of 100% in indomethacin-induced ulcer model, with no ulcers observed as compared to that of cimetidine, which offers a healing effect of 60.5%.Conclusion:The antiulcer activity of camel milk and urine may be attributed to its cytoprotective mechanism and antioxidant properties.SUMMARY Acute toxicity findings revealed the dosage of 10 ml/kg of camel milk and urine seems no toxic and indicating the dosage of 5 ml/kg is safe to be administered to the ratsOral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk (5 ml/kg) significantly inhibited gastric lesions by 83.7, 60.5 and 100% in the HCl/EtOH experimental modelThe results of this investigation have proven that camel milk and urine showed strong ulcer healing effect in indomethacin-induced gastric damage. Abbreviations used: NSAIDs: Non-steroidal anti-inflammatory drugs, UI: Ulcer index, ANOVA: One-way analysis of variance, WRS: Water-restraint stress, ROS: Reactive oxygen species

The influence of oral cimetidine administration on creatinine clearance in chilren with chronic renal failure: A preliminary study

Background Serum creatinine and creatinine clearance are usedto assess glomerular filtration rate but have a major disadvantagesince a variable amount of creatinine is secreted in the proximaltubule. This may cause an unpredictable overestimation of GFR.Tubular creatinine secretion can be blocked by cimetidine throughcompetitive inhibition of cation transport in the proximal tubularluminal membrane.Objective Cimetidine administration might improve the reliabilityof creatinine as a marker of glomerular filtration.Methods A preliminary study with a one-group pretest-posttestdesign in 11 children with chronic renal failure. Serum cystatin Clevel as reference value was compared with creatinine clearancemeasured before and after oral ingestion of cimetidine. The doseof cimetidine was adjusted with the GFR using Schwartz formula.Statistical evaluation was done with the Wilcoxon signed rankstest.Result The mean creatinine clearance before cimetidine adminis-tration was 27.4 (SD 14.6) ml/minute/1.73 m 2 BSA, and decreasedafter cimetidine to 21.1 (SD 13,1) ml/minute/1.73 m 2 BSA (p=0.015).Conclusion Oral cimetidine was effective in inhibiting creatininetubular secretion. This study could not prove that cimetidine im-proves the accuracy of creatinine clearance

A randomized, placebo-controlled, double-blind phase II trial of peri-operative cimetidine in early colorectal cancer.

509 Background: A Cochrane meta-analysis of randomised trials using histamine-type 2 receptor antagonists with surgery for colorectal cancer (CRC) demonstrated a hazard ratio of 0.53 for mortality if patients used cimetidine. The benefit is likely to be specific to patients whose tumours express the antigens that allow circulating cells to bind to endothelial selectin (E-selectin), the expression of which is induced by inflammatory cytokines perioperatively and inhibited by cimetidine. This trial sought to evaluate several key issues critical to informing the conduct of a phase 3 trial. Methods: Patients with non-metastatic CRC planned for curative-intent surgery were randomised to receive cimetidine 800mg BID or placebo orally for 5 weeks, starting 2-7 days preoperatively. A subset of patients had serial blood sampling for inflammatory cytokines. In addition to DFS and OS, endpoints assessed include treatment compliance and toxicity, recruitment issues, post-operative stay and complications, and tumour characteristics including expression of sialyl Lewis antigens and COX-2. Results: 123 patients (36% female) have been recruited in 4 centres over 3.5 years; another 4 are required to complete the planned 120 treated patients. The primary tumour was rectal in 45% and pathological postoperative tumour stage was 0-I, II, III, and IV in 29%, 33%, 35%, and 2% respectively. About 50% of CRC patients were eligible and fewer than half of those were recruited. Patient compliance was excellent with 89% of patients taking their medication orally in the first 2 days postoperatively. Inflammatory cytokines were commonly elevated postoperatively for up to 2 weeks but normalised by 4 weeks. Immunostaining for tumour antigens is in progress and will be presented. DFS and OS data are immature. Conclusions: Oral administration of cimetidine for 5 weeks is well-tolerated and feasible over the perioperative period, and covers the duration of elevated inflammatory cytokines. Correlative immunostaining studies will be presented. Clinical trial information: 12609000769280.

Whole-body physiologically based pharmacokinetic population modelling of oral drug administration: inter-individual variability of cimetidine absorption

Abstract Objectives Inter-individual variability of gastrointestinal physiology and transit properties can greatly influence the pharmacokinetics of an orally administered drug in vivo. To predict the expected range of pharmacokinetic plasma concentrations after oral drug administration, a physiologically based pharmacokinetic population model for gastrointestinal transit and absorption was developed and evaluated. Methods Mean values and variability measures of model parameters affecting the rate and extent of cimetidine absorption, such as gastric emptying, intestinal transit times and effective surface area of the small intestine, were obtained from the literature. Various scenarios incorporating different extents of inter-individual physiological variability were simulated and the simulation results were compared with experimental human study data obtained after oral cimetidine administration of four different tablets with varying release kinetics. Key findings The inter-individual variability in effective surface area was the largest contributor to absorption variability. Based on in-vitro dissolution profiles, the mean plasma cimetidine concentration–time profiles as well as the inter-individual variability could be well described for three cimetidine formulations. In the case of the formulation with the slowest dissolution kinetic, model predictions on the basis of the in-vitro dissolution profile underestimated the plasma exposure. Conclusions The model facilitates predictions of the inter-individual pharmacokinetic variability after oral drug administration for immediate and extended-release formulations of cimetidine, given reasonable in-vitro dissolution kinetics.

Whole-body physiologically based pharmacokinetic population modelling of oral drug administration: inter-individual variability of cimetidine absorption

Inter-individual variability of gastrointestinal physiology and transit properties can greatly influence the pharmacokinetics of an orally administered drug in vivo. To predict the expected range of pharmacokinetic plasma concentrations after oral drug administration, a physiologically based pharmacokinetic population model for gastrointestinal transit and absorption was developed and evaluated. Mean values and variability measures of model parameters affecting the rate and extent of cimetidine absorption, such as gastric emptying, intestinal transit times and effective surface area of the small intestine, were obtained from the literature. Various scenarios incorporating different extents of inter-individual physiological variability were simulated and the simulation results were compared with experimental human study data obtained after oral cimetidine administration of four different tablets with varying release kinetics. The inter-individual variability in effective surface area was the largest contributor to absorption variability. Based on in-vitro dissolution profiles, the mean plasma cimetidine concentration-time profiles as well as the inter-individual variability could be well described for three cimetidine formulations. In the case of the formulation with the slowest dissolution kinetic, model predictions on the basis of the in-vitro dissolution profile underestimated the plasma exposure. The model facilitates predictions of the inter-individual pharmacokinetic variability after oral drug administration for immediate and extended-release formulations of cimetidine, given reasonable in-vitro dissolution kinetics.

Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tablets

Long-term oral treatment with cimetidine is recommended to reduce vomiting in dogs with chronic gastritis. Despite this, few studies have specifically examined the plasma disposition and pharmacokinetics of cimetidine in dogs, particularly following repeated oral administration. The pharmacokinetics of cimetidine following oral administration as tablets was investigated in healthy dogs. Cimetidine was absorbed rapidly post-treatment (t(max) = 0.5 h). A mean absolute bioavailability of 75% was calculated following a single oral administration of 5 mg cimetidine/kg body weight. After intravenous administration, a plasma half-life of 1.6 h was calculated. Repeated oral administration at the recommended dose rate and regime (5 mg/kg body weight three times daily) for 30 consecutive days did not lead to any accumulation of cimetidine in plasma. Food intake concomitant with oral administration of cimetidine delayed (t(max) = 2.25 h) and decreased the rate and extent of absorption (AUC) by about 40%. Cimetidine was well absorbed in fasted dogs. Administration of food decreased the bioavailability of cimetidine by 40%. Cimetidine does not accumulate over time in plasma when administered long term to dogs.

Comparative study of the speed of acid‐suppressing effects of oral administration of cimetidine and famotidine

H2 histamine receptor antagonists (H2RAs) are widely used in patients with acid-related diseases, and the onset of antisecretory activity of H2RAs is reported to be faster than that of proton pump inhibitors (PPIs). The aim of this study was to compare the rapidity of onset of antisecretory activity of cimetidine and famotidine when orally administered. Fifteen healthy male Japanese volunteers (five H. pylori-positive and 10 H. pylori-negative) participated in a randomized cross-over study. All subjects were examined three times by ambulatory 6-h pH monitoring (from 17:30 to 23:30) with no medication or oral administration of 400 mg of cimetidine or 20 mg of famotidine. Drugs were administered at 19:30 after eating a standard meal, and plasma concentrations were also examined for 4 h periods. The plasma concentration of cimetidine increased rapidly after oral administration, while that of famotidine increased gradually. Intragastric pH was increased and percentage time with pH < 4.0 decreased significantly 2 h after administration of either cimetidine or famotidine. There was no statistically significant difference in acid-suppressing effect between cimetidine and famotidine during the short-term post-administration period. Rapidity of antisecretory activity did not differ between oral cimetidine and famotidine administered orally.

Influence of aging on gastric ulcer healing activities of cimetidine and omeprazole

In this study, we compared the effects of cimetidine and omeprazole on the healing of acetic acid-induced gastric ulcers in 8-, 48-, and 96-week-old rats. The repeated oral administration of cimetidine or omeprazole for 14 consecutive days markedly accelerated the ulcer healing in 8- and 48-week-old rats. However, both drugs were ineffective in 96-week-old rats. The basal gastric acid secretion of 8-, 48-, and 96-week-old rats decreased with aging. A single oral administration of cimetidine or omeprazole strongly decreased basal gastric acid secretion in the three different ages of rats. Cimetidine and omeprazole produced a potent and sustained serum gastrin-elevating action in 8- and 48-week-old rats. However, the gastrin-elevating actions of both drugs in 96-week-old rats were much weaker than in the 8- and 48-week-old rats. These results indicate that cimetidine and omeprazole have potent gastric ulcer healing actions in 8- and 48-week-old rats, as well as potent serum gastrin-elevating actions, but both drugs are ineffective in 96-week-old rats, which have lost their gastrin-elevating actions.

Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: correlation with antral gastric motility

The role of gastrointestinal motility and pH in determining cimetidine bioavailability as well as double peaks in plasma profiles following oral administration, in the quiescent or active phase of antral motility, to humans in the fasted state was examined. Plasma cimetidine-time curves did not show the presence of double peaks in any subject following intravenous administration. The incidence of double peaks was 73% following oral administration and was independent of antral migrating motility complex phase. Further, it was found that oral administration of cimetidine in the quiescent phase resulted in significantly higher bioavailability and in other pharmacokinetic parameters compared to that obtained following administration in the active phase. Excellent linearity in plots of motility peaks vs. plasma peaks with slopes close to unity were evident for both quiescent ( r 2=0.93) and active phase ( r 2=0.97) administration. A total of 14 peaks out of 22 (10 subjects, 64%) and 20 out of 27 peaks (11 subjects, 74%), were accounted for in quiescent and active phase oral administration, respectively. The proximal occurrence of plasma peaks to antral motility peaks typical of phase III contractions strongly implies that motility patterns may be responsible for secondary maxima following oral cimetidine administration in the fasted state.

Cimetidine administration and tubular creatinine secretion in patients with compensated cirrhosis

Cimetidine inhibits the tubular secretion of creatinine, without altering the glomerular filtration rate (GFR). During cimetidine administration the creatinine/inulin clearance ratio approaches unity in patients with renal failure. We determined the clearance of lithium (an index of fluid delivery to the distal nephron), inulin (a measure of the actual GFR) and creatinine during cimetidine administration to investigate the occurrence of tubular creatinine secretion in patients with compensated cirrhosis. A total of 12 patients with Child-Pugh A cirrhosis were studied initially. The subjects consumed a stable diet containing 100 mmol of sodium. On successive days, 9 h creatinine clearances were measured, first without and then with the oral administration of cimetidine (400 mg as a priming dose, followed by 200 mg every 3 h). During the first study day, 4 h renal lithium clearance was also calculated. A further group of five patients with fully compensated cirrhosis underwent the measurement (on successive days) of plasma inulin clearance, first without and then with the oral administration of cimetidine (same schedule of drug administration). Cimetidine administration unmasked a marked overestimation of GFR when calculated as creatinine clearance (baseline, 138+/-20 ml/min; +cimetidine, 89+/-13 ml/min; P<0.01). Consequently, during cimetidine administration the calculated lithium fractional excretion (a measure of the fraction of filtered sodium load that is delivered to the loop of Henle) rose from 21.4+/-13.2% to 32.3+/-18.9% (P<0.05), and the ratio between absolute distal tubular sodium reabsorption and filtered sodium load rose from 20.6+/-13.1% to 31.6+/-19.3% (P<0.01). Cimetidine caused no significant decrease in the actual GFR (i.e. inulin clearance) when administered to the second group of patients with compensated cirrhosis. Our data demonstrate significant tubular secretion of creatinine in patients with compensated cirrhosis and, consequently, a marked overestimation of GFR and filtered sodium load and an underestimation of the fractional distal tubular sodium reabsorption when these parameters are calculated by means of the traditional creatinine and lithium clearance computation. The true GFR (measured as inulin clearance) is unaffected by cimetidine administration.

Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in clinically normal milk-fed calves.

To characterize the change of pH in the abomasal lumen throughout a 24-hour period, to determine whether pH of the abomasal body differs from pH of the pyloric antrum, and to determine whether oral administration of cimetidine and ranitidine alters pH of the abomasal lumen in milk-fed calves. 5 male dairy calves (4 Holsteins-Friesian, 1 Ayrshire), 5 to 15 days old. Cannulas were surgically positioned in the abomasal body and pyloric antrum of each calf. Calves received the following treatments in a randomized crossover design: milk replacer (60 ml/kg of body weight, q 12 h [untreated control calves]), milk replacer and cimetidine (50 or 100 mg/kg, q 8 h), or milk replacer and ranitidine (10 or 50 mg/kg, q 8 h). The pH of the abomasal body and pyloric antrum was measured for 24 hours, using miniature glass pH electrodes. Suckling of milk replacer immediately increased abomasal luminal pH from 1.4 to 6.0, followed by a gradual decrease to preprandial values by 6 hours. Preprandial and postprandial pH values were not significantly different between the abomasal body and pyloric antrum, indicating lack of pH compartmentalization in the abomasum of milk-fed calves. Administration of cimetidine and ranitidine caused a significant dose-dependent increase in mean 24-hour abomasal luminal pH. Abomasal acid secretion in milk-fed calves is mediated in part by histamine type-2 receptors. Cimetidine and ranitidine may be efficacious in the treatment of abomasal ulcers in milk-fed calves.

Assessing Renal Function From Creatinine Measurements in Adults With Chronic Renal Failure

Abstract Measurement of glomerular filtration rate (GFR) following the injection of one of several suitable marker substances remains the best method to determine the severity of renal insufficiency as well as its rate of progression. However, the expense of these procedures continues to restrict their use. A second alternative is the determination of creatinine clearance (CCr) after oral administration of cimetidine. This drug blocks tubular secretion of creatinine almost completely, and CCr measured under these conditions is reported to be nearly identical to GFR in mild or severe renal failure. The optimal dose and timing of cimetidine for this purpose is still uncertain, but a single 1,200-mg dose 2 hours before beginning urine collection is probably suitable. A third alternative is simply the measurement of serum or plasma creatinine (PCr) concentration. However, it is well established that substantial reductions in renal function may occur before PCr becomes abnormal. GFR in adults with chronic renal failure can be approximately estimated from PCr, provided it is greater than 2 mg/dL, with the aid of additional demographic and biochemical variables. Gender, height, weight, age, and race should be taken into account. Further study is needed to derive the best formula for predicting GFR from PCr and other variables. Finally, CCr (without cimetidine) is still in use. This is unfortunate because it has been established that rather than improving on the estimation of GFR from PCr, CCr (determined from urinary creatinine measurements as well as PCr) is a less reliable guide to GFR than PCr alone. The CCr/GFR ratio is almost always greater than unity and increases with decreasing GFR to a maximum of approximately 1.7 at a GFR of approximately 20 mL/min. Furthermore, the variability of CCr is greater than that of PCr. Measurement of CCr (without cimetidine) is an anachronism and should be abandoned. (Am J Kidney Dis 1998 Jul;32(1):23-31)

Assessing renal function from creatinine measurements in adults with chronic renal failure

Measurement of glomerular filtration rate (GFR) following the injection of one of several suitable marker substances remains the best method to determine the severity of renal insufficiency as well as its rate of progression. However, the expense of these procedures continues to restrict their use. A second alternative is the determination of creatinine clearance (CCr) after oral administration of cimetidine. This drug blocks tubular secretion of creatinine almost completely, and CCr measured under these conditions is reported to be nearly identical to GFR in mild or severe renal failure. The optimal dose and timing of cimetidine for this purpose is still uncertain, but a single 1,200-mg dose 2 hours before beginning urine collection is probably suitable. A third alternative is simply the measurement of serum or plasma creatinine (PCr) concentration. However, it is well established that substantial reductions in renal function may occur before PCr becomes abnormal. GFR in adults with chronic renal failure can be approximately estimated from PCr, provided it is greater than 2 mg/dL, with the aid of additional demographic and biochemical variables. Gender, height, weight, age, and race should be taken into account. Further study is needed to derive the best formula for predicting GFR from PCr and other variables. Finally, CCr (without cimetidine) is still in use. This is unfortunate because it has been established that rather than improving on the estimation of GFR from PCr, CCr (determined from urinary creatinine measurements as well as PCr) is a less reliable guide to GFR than PCr alone. The CCr/GFR ratio is almost always greater than unity and increases with decreasing GFR to a maximum of approximately 1.7 at a GFR of approximately 20 mL/min. Furthermore, the variability of CCr is greater than that of PCr. Measurement of CCr (without cimetidine) is an anachronism and should be abandoned. (Am J Kidney Dis 1998 Jul;32(1):23-31)

Administration of a histamine 2-receptor antagonist in reflux esophagitis after gastrectomy: simultaneous pH monitoring of the esophagus and residual stomach

Some patients with protease inhibitor-resistant reflux esophagitis after distal or proximal gastrectomy may need an acid secretion inhibitor. Clinicians, however, often hesitate to administer histamine 2-receptor antagonists (H 2RAs) in reflux esophagitis after distal or proximal gastrectomy. If H 2RAs raise intraesophageal pH values in alkaline exposure cases, reflux esophagitis after gastrectomy will probably worsen. In the present study, 14 patients underwent simultaneous gastroesophageal pH monitoring to investigate the pathogenesis of reflux esophagitis after gastrectomy and the effect of H 2RA administration in alkaline exposure cases. One patient had a previous proximal gastrectomy and complained of acid reflux. Twelve (92.3%) of the 13 patients with reflux esophagitis after distal gastrectomy were considered alkaline exposure cases without acid reflux, but there was one patient in whom acid reflux was seen. Continuation of the esophageal alkaline exposure after acidification of the residual stomach was seen in alkaline exposure cases. Oral administration of cimetidine 400 mg twice (800 mg total) increased the pH of the residual stomach but did not affect the pH of the esophagus in patients with alkaline exposure. The study suggests that administration of an H 2RA in alkaline exposure cases may not worsen esophagitis and is not contraindicated for reflux esophagitis after distal gastrectomy.

Treatment of refractory interstitial cystitis.

Interstitial cystitis is the most therapeutically frustrating condition of the urinary tract. The vast array of treatments available clearly indicates that none is particularly effective. As the majority of patients fail to experience a significant and prolonged response to standard treatments, new options are frequently being developed. These include the oral administration of cimetidine, the intravesical use of hyaluronic acid and BCG, and total cystectomy with the formation of a continent urinary diversion. Unfortunately, the acceptance of many new treatments is based on incomplete evaluation, and this has resulted in a confusing array of disparate alternatives. Effective and durable treatment will not be available until the nature of the disease is better understood and the mechanisms of action of current therapies are elucidated.

Effect of a combination of ecabet sodium and cimetidine on experimentally induced gastric lesions and gastric mucosal resistance to ulcerogenic agents in rats.

We studied the effect of single oral administration of ecabet sodium (ecabet), a gastroprotective agent, in combination with the histamine H2-receptor antagonist cimetidine on gastric acid secretion, mucosal prostaglandin E2 (PGE2) production and experimentally induced acute hemorrhagic gastric lesions in rats. The effect repeated administration of ecabet in combination with cimetidine on the vulnerability of gastric mucosa to the ulcerogenic agents 0.6N HCl and aspirin was also studied. In pylorus-ligated rats, oral administration of cimetidine reduced gastric acid secretion, whereas ecabet did not affect the cimetidine-induced reduction in acid secretion. On the other hand, ecabet increased the capacity of gastric mucosa to synthesize PGE2, while cimetidine showed no effect on this parameter either in the presence of absence of ecabet. Both ecabet and cimetidine inhibited the formation of aspirin-induced gastric mucosal lesions, and the combination of ecabet and cimetidine showed a more potent inhibition than either drug alone. After cessation of repeated administration of cimetidine, but not ecabet, the 0.6N HCl- and aspirin-induced gastric lesions were significantly aggravated. The co-administration of ecabet improved the cimetidine-induced aggravation of these gastric lesions. These results suggest that ecabet in combination with cimetidine augments the antiulcer effect of cimetidine and improves the cimetidine-induced increase in gastric mucosal vulnerability to the ulcerogenic agents.

Cimetidine and omeprazole accelerate gastric ulcer healing by an increase in gastrin secretion.

Daily oral administration of cimetidine or omeprazole markedly accelerated the healing of acetic acid-induced gastric ulcers in rats with a limited food intake time. The increased gastric acid secretion induced by daily treatment with histamine affected neither the spontaneous healing of the ulcers nor the healing-promoting actions of both agents. Pretreatment of rats with ulcers with 6-hydroxydopamine significantly inhibited the increase in the antrum gastrin cells, serum gastrin levels and corpus mucosal thickness elicited by repeated administration of cimetidine or omeprazole. Pretreatment with 6-hydroxydopamine did not affect the inhibitory actions of cimetidine and omeprazole on acid secretion, but completely abolished the ulcer healing-promoting actions of both drugs. Daily intraperitoneal administration of pentagastrin accelerated ulcer healing. These results suggest that cimetidine and omeprazole mainly accelerate the healing of gastric ulcers by the trophic action of gastrin via the increase in gastrin secretion, while the inhibition of acid secretion may play a minor role in ulcer healing.

Investigations into the chirality of the metabolic sulfoxidation of cimetidine

AbstractThe individual enantiomers of cimetidine sulfoxide were resolved by preparative chromatography using a Chiralcel OC stationary phase and were characterized by the determination of optical rotation and circular dichroism spectra. Cimetidine sulfoxide was isolated from the urine of two healthy male volunteers following oral administration of cimetidine (400 mg). Urine was collected every 2 h for 12 h postdosing, after which time HPLC analysis indicated negligible recovery of the drug as the sulfoxide. Some 7% of the dose was recovered as cimetidine sulfoxide over this period. The enantiomeric composition of cimetidine sulfoxide was determined by sequential achiral—chiral chromatography using the OC phase. Over the collection period the enantiomeric ratio was found to be constant in all samples at (+/−) of 71 ± 2.5:29 ± 2.5. The enantiomeric composition of cimetidine sulfoxide was also determined in rat urine (24 h) following the administration of cimetidine (30 mg/kg po) to male Wistar rats (n = 7). The enantiomeric ratio in this case was found to be (+/−) 57 ± 2.3:43 ± 2.3. These preliminary data indicate that sulfoxidation of cimetidine is stereoselective with respect to the (+)‐enantiomer and that species variation in enantiomeric composition occurs. © 1994 Wiley‐Liss, Inc.

The Effect of Cimetidine on Verruca Plana Juvenilis: Clinical Trials in Six Patients

Cimetidine is an H2-receptor antagonist which is mainly used to treat gastrointestinal diseases. Recently, many authors have suggested that cimetidine has the ability to reverse acquired tolerance to dinitrochlorobenzene (DNCB). We have used cimetidine in six patients with verruca plana who showed no therapeutic response to DNCB. Four of them responded and showed complete disappearance of the verruca plana. The mean duration of oral cimetidine administration (1.2 g/day) was 4 weeks until the disappearance. Therefore, we suggest that oral cimetidine can be used as an effective and safe adjunctive modality for the treatment of verruca plana.