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Objective: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage., Methods: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals., Results: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals., Conclusion: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Vitacel M80K, a cellulose powder coated with 2% colloidal silica, is a recently developed direct compressible vehicle (DCV). The aim of this study is to investigate the performance of M80K, in comparison with: a laboratory prepared vehicle (ELC+) consisting of a mixture of Elcema P050 (ELC) and 2% Aerosil, and a microcrystalline cellulose (MCC), Avicel PH 101 (Avicel). Bulk density, flow and surface characteristics of the DCVs were determined. Tablets were prepared by direct compression using various drugs; ascorbic acid (fine and coarse crystals), cimetidine, and paracetamol. Tablets prepared with M80K showed less weight variation than those prepared with Avicel. Ascorbic acid-Avicel tablets were slightly harder than those with M80K. However, in the presence of either cimetidine or paracetamol, M80K resulted in the production of tablets with maximum hardness. In most cases, except with paracetamol, M80K produced tablets with slightly higher friability in comparison to Avicel, while ELC+ showed maximum friability. M80K-paracetamol tablets showed the minimum friability values and highest hardness sensitivity towards increase of the applied compression force between 5 and 35 kN. M80K-containing formulations showed better hardness tolerance upon the addition of magnesium stearate. Disintegration times for most tablets were relatively short (<5 min)., (Copyright 1998 Elsevier Science B.V.)

An in vivo micronucleus assay using Balb/C male mice was used to examine antigenotoxic effects of cimetidine (CM) on benzene (BZN) induced genotoxic effects. CM not only has therapeutic and immunomudolatory role, but it has also been shown to protect bone marrow stem cells from radiation induced clastogenic effects. Therefore, in the present study we attempt to investigate the protective effects and possible mechanisms involved in the effects of CM. An 8-week-old male Balb/C mice (22+/-4 g weight) were treated with different doses of BZN (400, 600 and 800 mg/kg body weight), i.p. and sampled at 24, 48 and 72 h after treatment by cervical dislocation. Various doses of CM (10, 15, 30 mg/kg) were used in association with BZN and 1-2 h prior to BZN treatment. Results show that BZN effectively induced micronuclei in polychromatic erythrocytes (PCEs). Application of CM led to a significant reduction of micronuclei in PCEs, i.e. 2-fold after 10 mg/kg and 3-fold after 30 mg/kg CM treatment. Results also indicate CM was more effective when used in combination with BZN. Therefore, results indicate that CM could reduce clastogenic effects of BZN. Although further investigations are needed to reveal the mechanistical background behind the effect, the most probable mechanism involved might be free radical scavenging. This mechanism might be associated with amplification of glutathione system and cytochrome P-450 inhibition.

Aim: To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on demand for relief of typical symptoms of gastro-oesophageal reflux disease during a 15-day period., Methods: A total of 1336 patients (aged > or = 18 years) with heartburn episodes were recruited and randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group. Depending on the occurrence or persistence of heartburn, treatment was administered as required up to three times daily, with at least 2 h between drug doses. Antacids were allowed as rescue medication if symptoms persisted for at least 2 h after the third medication on any given day. The primary end-point was defined as the proportion of patients with relief of at least 75% of heartburn episodes during the study period (i.e. relief occurring within 2 h after drug ingestion and lasting for at least 5 h)., Results: Analysis was performed in an intention-to-treat population comprising 504 subjects in the ranitidine group, 515 in the cimetidine group and 270 in the placebo group. Primary end-point success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001 for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine 75 mg was significantly more effective than placebo in providing overall heartburn relief (P < 0.001). The differences between the ranitidine and cimetidine groups were not significant, except for a greater reduction in heartburn frequency in the ranitidine group at the end of the study period (P < 0.05). Drug dose was lower and less rescue medication was used in the ranitidine group than the placebo group. The three treatment groups did not differ in terms of tolerability., Conclusion: On-demand ranitidine 75 mg or cimetidine 200 mg are safe and effective treatment for reflux-related symptoms.

Objective: Depressive effects of cardiopulmonary bypass on cell-mediated immune responses may lead to postoperative infectious complications. We previously reported that cimetidine reduced postbypass depression of the cytotoxic activity of natural killer cells. This study evaluated cimetidine as an agent to preserve cellular immunity after cardiac operations., Methods: In a prospective randomized study, 20 patients were divided into two groups of equal size. Cimetidine-group patients received 400 mg of cimetidine intravenously before bypass and a 33 mg/hr intravenous infusion of cimetidine after the operation, continuing until the fifth postoperative day. Control-group patients received conventional perioperative therapy. Lymphocyte subsets, natural killer cell activity, percentage of CD56+CD16+ (percentage of natural killer cells), and percentage of CD11b+CD8+ (percentage of suppressor T lymphocytes) were measured perioperatively., Results: Although temporary postoperative reductions in percentages of CD3+, CD4+, and CD56+CD16+ cells were observed in both groups, CD8+ percentages on postoperative day 1 and CD11b+CD8+ percentages on postoperative days 1 and 3 in the cimetidine group were significantly lower compared with those in the control group (p = 0.01,p = 0.004, andp = 0.02, respectively). Temporary postoperative reduction of natural killer cell activity was also observed in both groups, but the natural killer cell activity on postoperative day 1 in the cimetidine group (17.1%) was significantly higher (p = 0.02) than that in the control group (8.20%)., Conclusions: Cimetidine counteracts depressive effects of cardiopulmonary bypass on cell-mediated immunity and may possibly reduce postoperative susceptibility to infection.

Study Objective: To evaluate the effect of cimetidine, famotidine, ranitidine, and placebo on left ventricular systolic function, aerobic metabolic performance, and exercise capacity in patients with chronic, stable heart failure., Design: Double-blind, randomized, placebo-controlled, four-way crossover study., Setting: Outpatient, university-affiliated cardiology clinic., Patients: Twelve men with stable New York Heart Association class II or III heart failure secondary to ischemic heart disease or hypertension., Interventions: Patients received in random sequence cimetidine 400 mg twice/day, famotidine 40 mg/day, ranitidine 150 mg twice/day, and placebo. Each treatment was administered for 7 days, and the periods were separated by a 1-week washout., Measurements and Main Results: Before and after each treatment, patients underwent a bicycle stress echocardiogram with aerobic metabolic assessment. Left ventricular function was evaluated by calculating ejection phase indexes from Doppler echocardiographic measurements. All 12 patients successfully completed the study. No patient reported any adverse effect attributed to study drugs. None of the treatments was associated with significant changes in any measure of left ventricular systolic function, aerobic metabolic performance, or exercise capacity, nor were placebo-subtracted differences for the agents significantly different for any of the three measures., Conclusion: The three H2-receptor antagonists administered for 7 days at clinical dosages have no significant effect on left ventricular systolic function, aerobic metabolic performance, or exercise capacity in men with class II or III stable heart failure.

Prediction of the drug level in the volume of distribution was made using a numerical model taking into account the following facts: the kinetics of drug release out of the dosage form along the gastrointestinal tract, the kinetics of absorption in the blood compartment and the kinetics of elimination. Various parameters intervene significantly for a given dosage form. Some emphasis was placed upon the rate of elimination of the drug which appears to be the main characteristic for the drug, especially when it is delivered through controlled release dosage forms. The rate of release of the drug out of the dosage form, as well as the dose frequency and the gastrointestinal transit time were also considered. The drug level in the plasma was expressed by the amount of drug as a fraction of the amount of drug initially located in the dosage form.

Twelve healthy male volunteers participated in this open, randomized, placebo-controlled, two-way crossover study to investigate the effects of cimetidine on the steady-state pharmacokinetics of oral trovafloxacin. Volunteers were randomized to receive either 400 mg cimetidine twice daily or placebo for 5 days. From day 3-5, volunteers received 200 mg trovafloxacin once daily in addition to either cimetidine or placebo. After a minimum 7-day washout period, the study was repeated: those volunteers who received placebo during the first study period were administered cimetidine, and vice versa. The maximum observed serum trovafloxacin concentration, the area under the concentration-time curve of trovafloxacin within the dosing interval of 24 h and the earliest time to the maximum serum concentration for trovafloxacin in volunteers receiving concomitant cimetidine were 2.4 microg/ml. 27.8 microg x h/ml and 1.4 h, respectively, compared with 2.5 microg/ml, 27.1 microg x h/ml and 1.5 h, respectively, in volunteers receiving concomitant placebo. Thus. multiple dosing with cimetidine had no significant effect on the absorption or disposition of trovafloxacin at steady state. Co-administration of cimetidine and trovafloxacin was also well tolerated and without serious adverse effects.

Background: Amongst the low-dose H2-receptor antagonists available for the self-medication of dyspepsia, both famotidine 10 mg and cimetidine 200 mg have been shown to raise intragastric pH, but there is a delay after ingestion before significant effects can be demonstrated. A new effervescent preparation of cimetidine 200 mg releases an acid buffer which has a more rapid effect on intragastric pH., Aim: To investigate the relative abilities of low-dose famotidine and effervescent cimetidine to raise intragastric pH after a single postprandial evening dose., Methods: Twenty-four healthy subjects (12 men, 12 women, median age 32 years) completed a three-period crossover trial of famotidine 10 mg, effervescent cimetidine 200 mg and placebo. After a standard meal was given at 18.30 h to subjects fasted for 5.5 h, drug or placebo was given at 19.30 h. Intragastric pH was recorded with combined glass electrodes from 18.00 to 07.30 h by digital recorders., Results: Over the 12 h post-dose period the mean area under the pH/time curve (AUC) after famotidine 10 mg was 3.73, after cimetidine 200 mg effervescent 2.79, and after placebo 2.07. Over the same period the median pH and percentage of time that recordings were above pH 3 were 3.45 and 52.5 after famotidine 10 mg, 2.40 and 33.8 after cimetidine 200 mg effervescent, and 1.68 and 15.9 after placebo. Both active treatments were significantly different from placebo by each measure (P < 0.001), and famotidine 10 mg was significantly more effective than cimetidine 200 mg effervescent by each measure over the 0-12 h period (P < 0.001). Comparisons of mean AUCs for each 15 min period after dosing showed that decrease in acidity was significantly greater after cimetidine 200 mg effervescent than after famotidine 10 mg for the first 60 min. In the later post-dose period only famotidine 10 mg raised pH for all time points to 12 h, whilst the effect of effervescent cimetidine 200 mg was detectable to = 8 h., Conclusions: Inhibition of gastric acidity over the 12 h post-dose period was significantly greater and endured longer after famotidine 10 mg than after effervescent cimetidine 200 mg, but for the 60 min period immediately after dosing the effect on intragastric pH was significant following effervescent cimetidine 200 mg but not famotidine 10 mg. This suggests effervescent formulations of H2-receptor antagonists with an acid buffer have a more rapid effect on intragastric pH than film-coated tablets.

Aim: To compare the efficacy of cimetidine and tripotassium dicitrato bismuthate (TDB) in arthritic patients who had developed gastric (GU) or duodenal (DU) ulceration while taking non-steroidal anti-inflammatory drugs (NSAIDs)., Methods: Eighty-six rheumatoid arthritis (RA) patients affected by endoscopically proven DU (n = 44) or GU (n = 42), and on chronic NSAID therapy which was not suspended during anti-ulcer therapy, were randomized to cimetidine (400 mg t.d.s.) or TDB (120 mg q.d.s.). A repeat endoscopy was planned after 4 weeks (and 8 weeks, in case of failed healing). The patients who were unhealed after 8 weeks of therapy were allocated to the alternative anti-ulcer drug for a further 8 weeks without interrupting the anti-inflammatory therapy., Results: At week 4 of therapy. 14/24 (58%) DU and 9/20 (45%) GU patients treated with cimetidine were healed, compared with 12/20 (60%) and 10/22 (45%) TDB-treated patients (N.S.). At week 8 of therapy, the DU healing rates were 15/24 (63%) with cimetidine and 14/20 (70%) for TDB. The corresponding GU healing rates were 12/20 (60%) with cimetidine and 13/22 (60%) for TDB (N.S.). At week 16, complete healing with cimetidine was observed in 67% of DU and 57% of GU patients unhealed with TDB; the corresponding figures in the patients crossed to TDB were 83% for DU and 63% for GU patients (N.S. vs. cimetidine)., Conclusions: No statistically significant difference was found between the healing activities of cimetidine and TDB in rheumatoid arthritis patients with peptic ulcer who did not interrupt their NSAID treatment for arthritis. This trial showed that the continued consumption of NSAIDs appears to slow the ulcer healing process, especially in GU patients.

Objective: Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients., Research Design and Methods: In 30 outpatients with NIDDM and normo- (n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period., Results: Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 +/- 0.20 to 0.97 +/- 0.16 (means +/- SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 +/- 17.4 ml.min-1 (1.73 m2)-1, which decreased to -3.8 +/- 14.8 ml.min-1.(1.73 m2)-1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations., Conclusions: GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.

In clinical reality the drugs used for H1/H2-prophylaxis are not restricted to the combination of dimetinden/cimetidine, also only for this combination the effectiveness for preventing severe cardiorespiratory disturbances is proven in a randomised controlled clinical trial. However, it is almost impossible to conduct such an extended clinical trial in order to check all possible combinations. Instead of this, we developed a complex animal model featuring clinical variability and the principles of a well conducted randomised controlled clinical trial (CMRT = clinic modelling randomised trials), to evaluate different H1/H2 combinations. In this CMRT in pigs (four groups of 15 animals), the H1/H2 combination of dimetinden/cimetidine and dimetinden/famotidine showed an effectiveness similar to the randomised clinical trial. With dimetinden/ranitidine no significant prophylactic effect was observed. Two conclusions can be drawn: (1) CMRTs in animals are able to answer relevant clinical and research questions that otherwise only could be solved by clinical studies and may be a successful intermediate between basic research and clinical trials. (2) Drugs, even of the same substance class, may not be simply exchangeable. Hence, before changing a proven medication, trials in an adequate complex animal model (CMRT) should be mandatory.

Background/aims: Our investigations was carried out in order to examine the effect of cimetidine, ranitidine and famotidine on the generation of free radicals, lipid peroxidation and enzymatic antioxidative defense in the blood of patients with peptic ulcer disease, clinically diagnosed as gastric or duodenal ulcer., Methodology: 124 non-smoking males (aged 20-51 years), were randomly divided into 4 groups: 28 patients received intravenously 200 mg of cimetidine; 26 patients intravenously 50 mg comprised of ranitidine; 25 patients received intravenously 20 mg of famotidine; and 45 healthy men served as the control group. Superoxide dismutase activity, malonyldialdehyde concentration in blood platelets and superoxide anion generation in granulocytes were determined in all examined men. An assay of superoxide dismutase activity and malonyldialdehyde concentration were performed before drug administration and after 2 and 72 hours. Superoxide anion generation was estimated before drug administration and after 2 hours., Results: Our data indicate that all examined H2 receptor antagonists stimulate superoxide dismutase activity, but after 72 hours a distinct increase was observed, in addition to a decrease of malonyldialdehyde concentration. No differences have been observed in superoxide anion generation in patients with ulcer disease or in healthy subjects before and after ranitidine and famotidine administration. Only after 2 hours of cimetidine administration was a significant increase in superoxide anion generation observed., Conclusion: We concluded that H2 receptor antagonists have a beneficial effect on antioxidative processes.

Epirubicin is known to be metabolized in the liver. Therefore, drugs such as cimetidine, which inhibit the cytochrome P-450 enzyme system or reduce liver blood flow, may reduce the plasma clearance of epirubicin. In a small study, epirubicin 100 mg/m2 every 3 weeks was administered intravenously to eight patients, who also received oral cimetidine (400 mg b.d. for 7 days starting 5 days before chemotherapy) with either the first or second cycles. Epirubicin pharmacokinetics and liver blood flow (idocyanine green clearance) were assessed at each course. The areas under the plasma concentration time curves (AUCs) were used to compare the systemic exposure to epirubicin and its metabolites with each course. The estimated median percentage increase (95% confidence interval CI) in the AUC with cimetidine were: epirubicin 50% (95% CI -18 to 193, epirubicinol 41% (95% CI 1 to 92). Despite the small numbers studied, the increase in the active metabolite epirubicinol was significant (P < 0.05). These changes in exposure were not explained by reduced cytochrome P-450 activity as the 7-deoxy-doxorubicinol aglycone AUC was not reduced (357% increase: 95% CI 17 to 719) or by a decrease in liver blood flow (17% increase: 95% CI -39 to 104). Cimetidine is likely to be coprescribed or self-administered with epirubicin and therefore clinicians should be aware of this potential interaction.

The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (i.p.) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected i.p. with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immuno-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 +/- 18 to 164 +/- 13 ng/mL) and a parallel increase in lidocaine levels (from 73 +/- 22 to 172 +/- 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produce a significant decrease in MEGX levels (151 +/- 16 and 139 +/- 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with cimetidine produced a marked decrease in lidocaine levels (37 +/- 27 and 63 +/- 28 ng/mL, respectively) and no modification of MEGX levels (155 +/- 12 and 165 +/- 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

Background: There is documentation of the long-term use of omeprazole 10 mg o.d. in patients with reflux oesophagitis but not in the large number of gastrooesophageal reflux disease (GERD) patients without oesophagitis. There is also a paucity of data on the long-term use of cimetidine in GERD patients., Methods: One hundred and fifty-six patients (100 male) who previously had symptomatic non-ulcerative oesophagitis (81%) or symptoms without oesophagitis (19%), were recruited. All patients were in symptomatic remission following 4 weeks of omeprazole 20 mg o.d. or cimetidine 400 mg q.d.s. and, if required, a further 4 weeks of omeprazole 20 mg o.d. Patients were randomized to receive, double-blind, either omeprazole 10 mg o.m. (n = 77) or cimetidine 800 mg nocte (n = 79) for 24 weeks., Results: A greater proportion of patients receiving omeprazole, compared with cimetidine, were in symptomatic remission after 12 (69 vs. 27%) and 24 weeks (60 vs. 24%) (each P < 0.0001). The median time to symptomatic relapse was longer for patients receiving omeprazole (169 vs. 15 days) (P = 0.0001). Of patients leaving the study in symptomatic remission, a greater proportion receiving omeprazole, compared with cimetidine, was free of oesophagitis (84 vs. 53%) (P < 0.05)., Conclusion: Omeprazole 10 mg o.m. is more effective than cimetidine 800 mg nocte in the prevention of recurrence of GERD-associated heartburn and the occurrence of underlying oesophagitis.

Background: Erosive oesophagitis refractory to high dose histamine H2 receptor antagonists (definition: failure to heal fully after > or = 3 months' treatment with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg daily but frequently relapses when the patients are put back on maintenance H2 receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2 g, respectively)., Aim: To investigate the efficacy of maintenance omeprazole 20 mg daily in refractory erosive oesophagitis., Patients & Methods: In this open, sequential study, patients with H2 receptor antagonist-refractory oesophagitis were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole 40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily for up to 4.5 years., Results: Healing on omeprazole occurred in 38 out of 39 patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed (asymptomatic in half) during subsequent maintenance treatment, whereas all had relapsed earlier on high dose H2 receptor antagonists., Conclusion: Within the limits of interpretation of an open study, omeprazole 20 mg daily seems effective in maintaining prolonged remission in this group of patients with H2 receptor antagonist-refractory oesophagitis.

Cimetidine was administered intravenously and by the intragastric route to six mares at a dose of 4.0 mg/kg of body weight (bw). Specific and sensitive high performance liquid chromatographic methods for the determination of cimetidine in horse plasma and urine and cimetidine sulfoxide in urine are described. Plasma cimetidine concentration vs. time data were analysed by non-linear least squares regression analysis to determine pharmacokinetic parameter estimates. The median (range) plasma clearance (Cl) was 8.20 (4.96-10.2) mL/min.kg of body weight, that of the steady-state volume of distribution (Vdss) was 0.771 (0.521-1.15) L/kg bw, and that of the terminal elimination half-life (t1/2 beta) was 92.4 (70.6-125) minutes. The median (range) renal clearance of cimetidine was 4.08 (2.19-6.23) mL/min.kg bw or 55.4 (36.3-81.8)% of the corresponding plasma clearance. Cimetidine sulfoxide was excreted in urine and its urinary excretion through 8 h accounted for 12.0 (9.8-16.6)% of the plasma clearance of cimetidine. The median (range) extent of intragastric bioavailability was 14.4 (6.82-21.8)% and the maximum plasma concentration after intragastric administration was 0.31 (0.24-0.50) microgram/mL. Intravenous cimetidine had no effect on the disposition of intravenous phenylbutazone or its metabolites except that the maximum plasma concentration of gamma-hydroxyphenylbutazone was less after cimetidine treatment.

Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of N-acetylcysteine (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine and the two in combination, administered 2 h post-paracetamol dose, on mortality, plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activities and hepatic reduced glutathione (GSH) levels were investigated in mice 24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked reduction in plasma GOT and GPT activities to within the normal range, while significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore concluded that cimetidine and N-acetylcysteine may have an additive hepatoprotective action in the treatment of paracetamol overdose.

Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases. We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine. To test this hypothesis, a randomized placebo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart. Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two immunizations. All 14 volunteers completed the study with excellent compliance. Sera were tested for anti-OMP and bactericidal antibodies. The groups were comparable in terms of gender distribution, age and baseline anti-OMP titers. Reactogenicity to the vaccine was mild and comparable between groups. There was little effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels over time. Geometric means of maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine.

A retrospective analysis of prospectively collected data was performed to compare the frequency of upper gastrointestinal bleeding (GIB) in seriously burned patients treated with either cimetidine and antacids or enteral nutrition for ulcer prophylaxis. Five hundred and twenty-six seriously burned patients admitted to the burn intensive care unit of the BG Trauma Centre Ludwigshafen during a 4-year period were included into the study. All patients admitted to the burn unit from 1989 to 1991 received i.v. cimetidine (400 mg q4) for ulcer prophylaxis. If the intragastric pH dropped below 3.5, gastric pH was titrated with antacids up to > or = 4 via nasogastric tube. During the second 2-year period (1992-1993) early enteral nutrition alone was regarded to be ulcer protective and no further interventions for ulcer prophylaxis were routinely performed. Signs of overt upper GIB were monitored and documented through the entire study period. The overall occurrence rate of upper GIB in the cimetidine/antacids (C/A) group (n = 253) was 8.3 per cent with six cases of serious bleeding in five patients (1.98 per cent). In the enteral nutrition (EN) group (n = 273) the overall incidence of GIB was 3.3 per cent with two cases of serious bleeding (0.73 per cent). There were no deaths directly related to ulcer haemorrhage. The difference in the overall frequency of overt GIB between the groups studied was statistically significant (< 0.05). In our experience, early enteral nutrition is effective in the prevention of stress haemorrhage in the upper gastrointestinal tract. Additional medicinal prophylaxis is not required in burn patients.

The possible influence of Maalox 70, an antacid based on magnesium-aluminum hydroxide, and the H2-antagonist cimetidine, both commonly prescribed in hypercholesterolemic patients, on the pharmacokinetics of the new HMG-CoA reductase inhibitor cerivastatin was investigated in 2 separate studies in 8 healthy young male subjects each. Cerivastatin plasma concentration/time profiles were assessed by a specific HPLC assay; in addition, total immunoreactive drug (cerivastatin plus metabolites) was determined by RIA. Single oral doses of 200 micrograms cerivastatin were administered under fasting conditions without or with 10 ml Maalox 70 suspension. The mean AUC and Cmax ratios (combined dosing/monodosing) including 90% confidence intervals were 0.92 (0.73-1.15) and 0.89 (0.72-1.10) for the HPLC data, and 0.99 (0.85-1.14) and 1.03 (0.82-1.30) for the RIA data, respectively. Thus, no interaction of the simultaneous administration of Maalox 70 on the pharmacokinetics of cerivastatin was observed. In a similar controlled, randomized nonblind 2-way crossover design the influence of the H2- antagonist and well-known cytochrome P450 enzyme inhibitor cimetidine was investigated. Eight healthy young male volunteers received single oral doses of 200 micrograms cerivastatin alone or on the fourth day of a 4-day cimetidine 400 mg b.i.d. pretreatment. The mean AUC and Cmax ratios (combined dosing/monodosing) including 90% confidence intervals were 0.98 (0.90-1.08) and 0.91 (0.78-1.07) for the RIA data, and 0.89 (0.82-0.96) and 0.93 (0.80-1.09) for the HPLC data, respectively, clearly indicating that cimetidine and cerivastatin did not interact pharmacokinetically. These results do not only reflect the apparent insensitivity of cerivastatin absorption to possible changes in gastric pH, but demonstrate that the metabolic pathways of cerivastatin, involved in its first-pass metabolism and elimination, are rather insensitive to cytochrome P450 enzyme inhibition induced by cimetidine.

A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples were taken during a period of 12 h, and praziquantel concentration was measured by high-performance liquid chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during a period of 12 h; they increased 100% when cimetidine was jointly administered. Compared with other regimens, the high levels obtained and the longer duration of action seem to be advantageous in prolonging the exposure of the parasites to the drug and support previous clinical experience showing that the treatment of neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with the drug still retaining its cysticidal properties. Moreover, simultaneous administration of praziquantel and cimetidine could improve further the efficacy of the single-day therapy for cysticercosis and other parasitic diseases, such as schistosomiasis.

The combined effect of the histamine receptor antagonists Dexbrompheniramine (DXB: H1-receptor antagonist) and Cimetidine (C: H2-receptor antagonist) on food and water intake was investigated in pygmy goats. DXB (1 mg/kg BW0.75) and C (16 mg/kg BW0.75) were injected together intraperitoneally (i.p.). Cumulative food and water intake, as well as meal and draft pattern, were recorded. DXB and C significantly reduced cumulative water intake, whereas cumulative food intake did not change. Water to food ratio was also significantly diminished. Draft frequency and the percentage of drafts associated with meals were significantly reduced during the 6 h post injection, while meal frequency and meal size did not change during this period. The results show that blockade of the H1- and H2-histamine receptors attenuates the association between water and food intake in pygmy goats. Therefore, mechanisms responsible for meal-associated drinking seem to depend upon activation of histamine receptors.

Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl ] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is a novel H2-receptor antagonist with additional gastroprotective effect. The gastroprotective effect of oral doses of ebrotidine against ethanol-induced mucosal damage in female rats was compared with the effect of cimetidine, ranitidine and famotidine. Macroscopically, ebrotidine showed dose-dependent inhibition of the lesion, with significant differences from that of controls at doses of > or = 12.50 mg/kg (ED50 was 26.54 mg/kg). None of the other drugs tested showed gastroprotective effect under the same conditions. The histopathological study revealed significant reduction in the number of deep and superficial ulcers in ebrotidine-treated animals. The gastroprotective effect of ebrotidine is patent even in the presence of indometacin suggesting that prostaglandins play a rather negligible role in gastroprotective action. These results suggest that ebrotidine may be more useful than the classically known H2-antagonists in the treatment of peptic ulcers.

This paper reports the effects of the H2 antagonist cimetidine on the number of CD4+ and CD8+ cells in nasal mucosa and the IgE level of nasal secretions in patients with allergic rhinitis. The results showed the numbers of CD4+ cells were greater than the numbers of CD8+ cells in nasal mucosa, both in the patients with allergic rhinitis and normal subjects, but the ratio of CD4+:CD8+ cells was much higher in the patients with allergic rhinitis. After treatment with cimetidine locally for 4 weeks, the numbers of CD4+ cells fell and the numbers of CD8+ cells increased in the patients with allergic rhinitis. The high IgE level of nasal secretion of the patients with allergic rhinitis was much reduced after treatment with cimetidine. The results suggest that there are high numbers of CD4+ cells and lower numbers of CD8+ cells in the nasal mucosa and a high level of IgE in the nasal secretions of the patients with allergic rhinitis. Treatment with cimetidine locally may be of some value to relieve the clinical symptoms of allergic rhinitis.

We found indomethacin aggravates healed gastric ulcers (ulcer relapse) in rats. In the present study, we examined the effects of human basic fibroblast growth factor (bFGF) mutein CS23 (TGP-580) and histamine H2-receptor antagonists (H2-RAs) on ulcer relapse in this model. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Indomethacin (1 mg/kg/day) given s.c. for 2 weeks starting 4 weeks after the operation aggravated the healed ulcer; the areas with and without indomethacin were 4.8 +/- 1.4 and 0.4 +/- 0.3 mm2, respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administration period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/kg) and TGP-580 (0.1 mg/kg) for 4 weeks accelerated the healing. The aggravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. When the drugs were co-administered with indomethacin for 2 weeks, the aggravation was significantly prevented by ranitidine and mildly inhibited by cimetidine and TGP-580. Both TGP-580 and H2-RAs can prevent the ulcer relapse induced by indomethacin but via different modes of action: TGP-580 inhibits relapse mainly by acting on the process of healing, while H2-RAs act mainly on the process of aggravation.

Background: Serum ethanol concentrations may become higher when alcohol is consumed during treatment with histamine receptor antagonists, especially if ethanol is ingested postprandially. Only a few studies have investigated fasting subjects, and women have only been investigated sporadically., Methods: The present study compared serum ethanol concentrations after a 4-h fast followed by a low (0.15 g/kg) and a high (0.45 g/kg) dose of ethanol, on two separate occasions in six women and six men. The study was carried out before and after treatment with 400 mg cimetidine twice daily., Results: Cimetidine administration did not change the area under the concentration-time curve or the maximal serum ethanol concentration in either women or men, irrespective of ethanol dose. Ethanol elimination rate was unchanged by cimetidine., Conclusion: Cimetidine does not influence the ethanol concentration-time curve when ethanol is ingested on an empty stomach.

The dose-dependent hypotensive and bradycardic effects induced by an ichthyotoxic organophosphate compound isolated from the marine dinoflagellate Ptychodiscus brevis were studied. These effects were not antagonized by atropine, but potentiated by alpha-adrenoceptor blocker and hexamethonium. The toxin abolished the vasopressor effect elicited by phenylephrine, indicating an alpha-adrenergic blocking activity. The cardiovascular depressor responses were antagonized by tetraethylammonium while blockade of cholinergic and histaminergic receptors or inhibition of prostaglandin synthesis failed to modify these effects. The results indicate that the cardiovascular depressor effects of the toxin are probably mediated through alpha-adrenergic and ganglionic blockade accompanied by modulation of potassium channel activity.

The present study examined the effects of histamine in the guinea pig isolated vestibular hair cells (VHCs) by measuring the dynamic changes of intracellular free calcium ion ([Ca2+]i) concentration using calcium sensitive dye Fura-2. The histamine-induced calcium response in VHCs was markedly increased at the concentration of 10 microM histamine in the presence of extracellular Ca2+, while in the absence of extracellular Ca2+, a slow increase of [Ca2+]i was evident. Receptor specificity of the response to histamine was examined: promethazine (H1 receptor antagonist), cimetidine (H2 receptor antagonist) and thioperamide (H3 receptor antagonist) completely blocked the histamine-induced calcium response at the concentrations of 2.5 microM, 1.0 microM and 1.0 nM, respectively. The responses were mediated by H1, H2 and H3 receptors and resulted in a rise of [Ca2+]i due to an influx of Ca2+ from the extracellular space and a release from intracellular stores. Our preliminary data suggest that under immuno-pathological conditions of the inner ear, histamine released from the mast cells distributed in the endolymphatic sac may act through receptors located on the vestibular hair cell membrane and may regulate the cell function and the signal transduction in the vestibular nerve-hair cell afferent system.

Pretreatment with dopamine agonists (bromocriptine 2.5, L-dopa 2.5, apomorphine 0.05 mg/kg i.p.) and a histamine H2 receptor antagonist (cimetidine 50.0 mg/kg i.p.) was found to greatly reduce the haemorrhagic gastric lesions induced by 15-min pylorus ligation in rats. On the other hand, pretreatment with dopamine antagonists (haloperidol 5.0, sulpiride 1.0, domperidone 5.0 mg/kg i.p.) significantly aggravated these lesions. Cimetidine markedly diminished the ulcerogenic effect of haloperidol but not that of domperidone, suggesting a brain-mediated site for the protective interaction of cimetidine and dopamine systems.

Dapsone is a drug which is administered orally, on a daily basis, for four to five years as a cure for leprosy. The major problems associated with dapsone therapy include hemolysis, methemoglobinemia and patient non-compliance. Cimetidine reduces the side effects of dapsone and increases its levels in the blood. A ceramic drug delivery system was developed to maintain therapeutic levels of dapsone for an extended period of time and to alleviate associated side effects. In vitro release of commercial dapsone tablets (100 mg) and cimetidine pellets (400 mg) from hydroxyapatite reservoirs was studied in 100 ml absolute ethanol at 37 degrees C. Hydroxyapatite (HA) reservoirs loaded with one dapsone tablet released the drug at the rate of 8.3 mg/day for nine days, after which a much slower release occurred for another three days. With a load of two dapsone tablets, the rate of release was 6.7 mg/day for four weeks. HA reservoirs loaded with one cimetidine pellet delivered the drug at a rate of 25 mg/day for sixteen days. Combining both drugs in a single reservoir did not affect their respective release rates. When implanted subcutaneously in rats, HA reservoirs loaded with one dapsone tablet appeared to be well tolerated. After nine weeks, 77 mg of dapsone had been released. These experiments showed that HA reservoirs can be used to deliver dapsone and cimetidine in vivo.

Unlabelled: One hundred and six patients with active gastric ulcer proven by endoscopy were randomly allocated to receive cimetidine 800 mg at bedtime + teprenone 50 mg thrice daily; or cimetidine 800 mg at bedtime alone in a trial comparing the ulcer healing rate and the quality of healing at 4 or 8 weeks. At 4 weeks 72.4% (42/58) of those on cimetidine + teprenone and 52.1% (25/48) on cimetidine alone had ulcers healed in comparison of 93.1% (54/58) and 89.6% (43/48) respectively at 8 weeks. The difference was significant at 4 weeks, indicating the ulcer heal more rapidly in the combination therapy group. The stage S2 achievement rates were 34.5% (20/58) and 10.4% (5/48) at 4 weeks (P < 0.05), 50.0% (29/58) and 20.8% (10/48) at 8 weeks (P < 0.05) respectively, indicating the quality of ulcer healing was much better in the combination therapy group. The gastric mucosal hexosamine levels increase significantly after treatment (17.79 +/- 2.00 micrograms/mg) as compared to that before treatment (14.27 +/- 2.47 micrograms/mg) in the combination therapy group, indicating that teprenone stimulates macromolecular glycoprotein synthesis in gastric mucosa. This is thought to be a significant factor in the healing process of gastric ulceration., Conclusion: It is reasonable to administer teprenone, an agent increasing mucosal resistance, concurrently with H2 blockers in the treatment of active gastric ulcers.

Tissue hypoxia resulting from regional blood flow abnormalities and oxygen extraction defects may underlie the pathogenesis of multiple system organ failure (MSOF) in sepsis. Low-dose dopamine (LDD) is widely employed to enhance splanchnic perfusion although data to support this approach are lacking. We assessed the effect of LDD on surrogate markers of renal and gastric perfusion. Sixteen nonoliguric mechanically ventilated patients with sepsis syndrome received LDD (3 micrograms/kg/min) or placebo in a double-blind crossover design experiment. Hemodynamics, gastric intramucosal pH (pHi) urine volumes, urinary sodium excretion, and cimetidine-corrected creatinine clearance were compared. Mortality for the group was 63%. LDD caused a significant increase in urine volume (88 +/- 58 to 115 +/- 70 ml/h, p = 0.02, 95% confidence interval for change 4.7 to 49 ml/h), but no significant change in any other parameter. We conclude that use of LDD results in diuresis but does not improve other markers of renal or gut perfusion. These data do not support the use of LDD to reduce risk of progression to MSOF in sepsis.

Hemorrhagic stress ulceration (HSU), a known complication in the Surgical Intensive Care Unit (SICU) patient population, has a reported incidence rate of 25 to 75 per cent. The goal of this study was to evaluate whether the use of prophylactic antacid agents significantly reduced the frequency of HSU in critically ill patients, or whether improved care reflected the decrease in HSU. A total of 425 consecutive patients were reviewed for occurrence of HSU; of these, 304 were eligible for the study. Admitting diagnoses were trauma including head injury, postoperative patients, and patients with surgical complications. Inclusion criteria were length of stay in the SICU for at least 48 hours; antral gastric pH subsequently measured every 6 to 8 hours and maintained at > or = 4; and absence of the history of peptic ulcer disease or gastrointestinal bleeding. One group included 251 (83%) patients who were started on prophylactic agents (H2 blockers with or without antacids); the second group of 53 (17%) patients had no prophylaxis. The Injury Severity Score on admission to the SICU was 27.5 +/- 7.5, Apache II score was 26.4 +/- 6.4, and Revised Trauma Score was 4.3 +/- 2.3, with no difference in severity (P < 0.05). Thirteen (4%) patients were found to have evidence of HSU: 11 of 251 (4%) in the first group and 2 of 53 (4%) in the second. No statistically significant difference was found in the incidence of HSU between the two groups (P = 0.86). Results of this study suggest that modern prophylaxis for HSU did not significantly alter the incidence of stress ulceration in SICU patients.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been studied primarily on a 3-week schedule as a 3-, 24-, or 96-hour infusion at doses ranging from 135 to 250 mg/m2. The observed toxicity profile seems to be both dose and schedule dependent. Dose densification of paclitaxel given weekly over 6 weeks on a split-dose schedule for an overall increase in dose intensity was thought to improve the therapeutic index of paclitaxel in a variety of advanced malignancies and to be suitable for outpatient administration. For this study, chemotherapy consisted of a weekly 1-hour infusion of paclitaxel at a starting dose of 40 mg/m2/wk for 6 weeks, followed by a 2- to 3-week interval. Paclitaxel dosage was escalated in 10 mg/m2/wk increments in subsequent patients, to a maximum dosage of 90 mg/m2/wk. Intravenous dexamethasone, cimetidine, clemastine, and ondansetron were administered immediately before the paclitaxel infusion. Fifty patients participated in the study. The male to female ratio was 21 to 29, the median age was 53.2 years (age range, 33 to 74), and the median performance status was 1. All patients were chemotherapeutically pretreated. Overall response included five complete responses (10%), 15 partial responses (30%), 19 no change (38%), and 11 disease progressions (22%). Median dose intensity was 410 mg/m2/6 wk (range, 200 to 540 mg/m2/6 wk). Hematologic toxicity was mild, with no grade 3 or 4 toxicity up to 90 mg/m2/wk. No hypersensitivity reactions or neurologic or cardiac toxicities were documented. Dose-densified, weekly paclitaxel is concluded to be active in a variety of pretreated tumor entities. The overall low hematologic and peripheral toxicity profile suggests that further dose intensification of weekly paclitaxel and/or combination with other cytotoxic agents (eg, cisplatin/carboplatin, ifosfamide, etoposide) may be warranted. Paclitaxel can be given safely in the outpatient setting. Paclitaxel 90 mg/m2/wk is recommended for single-agent treatment. Dose-densified paclitaxel may be considered a valuable and promising alternative to standard 3-week treatment, with further options possible in combination chemotherapy.

Ranitidine 150 mg twice daily (BID) is an approved therapeutic approach for relieving the symptoms of gastroesophageal reflux disease. Ranitidine 150 mg four times daily (QID) and cimetidine 800 mg BID are indicated for endoscopically diagnosed erosive esophagitis. This 12-week, randomized, multicenter trial involving 696 patients compared ranitidine 150 mg BID and ranitidine 150 mg QID with cimetidine 800 mg BID in healing erosive esophagitis. Healing rates, as determined by endoscopy, at 4, 8, and 12 weeks were comparable with ranitidine 150 mg BID (38%, 56%, and 71%, respectively) and cimetidine 800 mg BID (37%, 52%, and 68%, respectively), as were reductions in heartburn frequency and antacid consumption. However, ranitidine 150 mg QID produced significantly higher healing rates (49%, 67%, and 77%, respectively) and greater reductions in heartburn frequency and antacid consumption than cimetidine 800 mg BID. All treatment regimens were well tolerated. Thus ranitidine 150 mg BID is as effective as cimetidine 800 mg BID, and ranitidine 150 mg QID is more effective than cimetidine 800 mg BID in healing erosive esophagitis and reducing heartburn frequency and antacid consumption.

Background & Aims: The gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are reduced by antisecretory agents. The effects of combination therapy on the gastrointestinal toxicity and therapeutic activity of free and phospholipid-associated NSAIDs were investigated in rats., Methods: Fasted rats, pretreated with either saline or an antisecretory dose of omeprazole, ranitidine, or cimetidine, were intragastrically administered saline, aspirin, or indomethacin. In ulcer models, gastric lesions in aspirin-treated rats and intestinal bleeding in indomethacin-treated rats were measured. For antipyretic and analgesic activity, rectal body temperature in febrile rats and the rats' pain sensitivity to pressure applied to an inflamed limb were measured, respectively., Results: NSAID-induced gastrointestinal ulceration and bleeding were reduced in rats pretreated with antisecretory agents and abolished in rats administered phospholipid-associated NSAIDs in combination with inhibitors of acid secretion. The antipyretic and analgesic activity of both NSAIDs was attenuated in rats pretreated with an antisecretory agent. This pH-dependent block in therapeutic activity was overcome if the NSAID was preassociated with a phospholipid to enhance the drug's lipophilic characteristics., Conclusions: Combination therapy of antisecretory agents and NSAIDs, chemically associated with phospholipids, has distinct advantages with regard to both low gastrointestinal toxicity and restored therapeutic activity.

There has been no effective therapy for metastatic renal cell carcinoma (RCC). Cimetidine has been demonstrated to block histamine mediated activation of suppressor T cells in man and in animal models, resulting in an anti-tumor immune response. We treated two patients with cimetidine for matastatic RCC. Case 1: A 61-year-old man presented with a diagnosis of metastatic lung and brain tumor of RCC. Interferon therapy was not effective, but after radiation therapy, his brain metastasis revealed partial response. He received cimetidine 800 mg orally after radiation, his lung metastasis revealed almost complete response. But he died of ischemic heart disease. Case 2: A 58-year-old woman presented with a metastatic lung tumor of RCC. We started interferon therapy. But because of general fatigue and anemia, she required discontinution of interferon therapy. So she received cimetidine 800 mg orally and her lung metastasis revealed complete response. She remained well and had no evidence of disease. Patients with metastatic renal cell carcinoma can occasionally respond to cimetidine and further investigation must be studied.

An HIV-positive adult presented with recalcitrant mucosal warts which failed to respond to therapies including curettage and cautery, cryocautery and oral etretinate. There was an apparent complete resolution of intra- and peri-oral warts with the histamine H2 antagonist, cimetidine.

Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparation in which this normally insoluble anti-hydatid drug is well solublilized in aqueous media. The high entrapment efficiency observed (75-87%) and the stability of the formulation make this a promising delivery vehicle for improved chemotherapy with albendazole. In particular, the high degree of association with phospholipid may give rise to increased oral bioavailability. Oral administration of albendazole in liposomes led to increased concentration and/or altered metabolism of albendazole sulphoxide (ABZSX) in liver and/or plasma in non-infected Wistar rats. Results from experiments using cotton rats (Sigmodon hispidus) infected with metacestodes of Echinococcus multilocularis show that entrapment within liposomes clearly increases the uptake of albendazole via the oral route. This was reflected by increased levels of albendazole and the two major metabolites in plasma, liver and cyst homogenate when a dose of liposomal albendazole (35 mg/kg) was given orally compared to free albendazole at 50 mg/kg. There was a 75-94% reduction in biomass of the metacestode and a significant increase in survival time for the animals treated with liposome entrapped albendazole. A clear difference in distribution of albendazole and its metabolites in the liver and the metacestode tissues in the presence of cimetidine indicated that the latter has a profound effect on the metabolism of albendazole. There appeared to be a synergistic interaction between albendazole and cimetidine, since the metabolism of albendazole was markedly altered in the combined cimetidine/ liposome-albendazole group, and higher therapeutic effect was observed. These findings indicate potential both for improvement of treatment of larval E. multilocularis infection and for reduction of albendazole dose levels.

Our purpose was to determine if oral cimetidine, a histamine-receptor antagonist, might be of benefit in the treatment of extensive molluscum contagiosum in children. We present 13 pediatric patients in whom conventional treatment modalities for molluscum contagiosum were unsuccessful or difficult to apply. They were treated with a two-month course of oral cimetidine 40 mg/kg/day. All but three children who completed treatment experienced clearance of all lesions. These children had no new lesions but had persistence of several lesions. One child did not take the drug and did not clear. No adverse effects were observed. We conclude that oral cimetidine may be of benefit in the management of widespread or facial molluscum contagiosum in immunocompetent children.

Cimetidine therapy used for the treatment of gastric bleeding due to tolazoline therapy in a newborn infant was temporally associated with episodes of severe hypoxemia. It appears likely that the histamine H2 receptor blocked by cimetidine obviated the pulmonary vasodilator effect of tolazoline therapy.

Background: Cimetidine, an H2-receptor antagonist, has been used successfully to treat patients with mucocutaneous candidiasis, common variable immunodeficiency, herpes simplex, and herpes zoster because of its immunomodulatory effects. Recently, some trials have suggested that cimetidine may also be useful for the treatment of warts., Objective: The aim of the present study was to determine whether cimetidine is effective in the treatment of warts., Methods: Seventy patients with multiple warts were included in a placebo-controlled, double-blind study. Patients were randomly allocated to treatment groups equally. The groups received cimetidine, 25 to 40 mg/kg daily, or placebo for 3 months. Patients were examined at monthly intervals., Results: At the end of the therapy, 28 cimetidine-treated and 26 placebo-treated patients were examined to determine the efficacy of treatment. Cure rates obtained were 32% (9 of 28) in the cimetidine-treated group and 30.7% (8 of 26) in the placebo-treated group. No significant difference was found between cimetidine and placebo in effectiveness (p = 0.85)., Conclusion: Our results show that cimetidine is no more effective than placebo in the treatment of patients with common warts.

Fifteen crossbred sheep were assigned randomly to 1 of 5 treatments: endophyte-free fescue diet (EF; 0% infected; 50% hay, 40% seed, 10% molasses); endophyte-infected diet (El; 95% infected; 50% hay, 40% seed, 10% molasses); El + 15 mg metoclopramide/kg body weight, 3 times/w; El + 9.0 mg cimetidine/kg body weight, twice daily; or El + metoclopramide + cimetidine. Both diets contained 92% dry matter (DM), 94% organic matter (OM) and 12% crude protein. All sheep were housed in individual metabolism stalls at 30 C, 14-h light:10-h dark for 18 d. Serum prolactin, respiration rate, heart rate or ear tip, coronary band and rectal temperatures were not affected by any of the treatments after 18 d (P > .10). No differences were detected in nutrient digestibilities except for treatment with metoclopramide + cimetidine, which produced decreased DM, OM and energy digestibilities. Sheep fed the El diet did not exhibit typical fescue toxicosis; therefore, the use of metoclopramide and(or) cimetidine to prevent toxicosis could not be evaluated.