Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease: an observation on non-absorbable antibiotics.

AIM: To estimate the prevalence of small intestine bacterial overgrowth (SIBO) among patients with an earlier diagnosis of irritable bowel disease (IBS) in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS: A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis. RESULTS: When the patients underwent a "breath test", 33 (45.2%) showed the presence of a SIBO. After treatment with rifaximin 1,200 mg/d for seven days in 32 patients, 19 (59.4%) showed a negative "breath test" one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, "breath test" remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative "breath test" in one patient only. CONCLUSION: (1) about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; (2) only a "breath test" with lactulose (or with glucose in subjects with an intolerance to lactose) can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and (3) the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.

Evaluation of rifaximin, placebo and lactulose in reducing the levels of benzodiazepine-like compounds in patients with liver cirrhosis: a pilot study.

Benzodiazepine-like compounds (BZDs), either taken with the diet or synthesized by intestinal bacterial flora, may represent a precipitating factor for hepatic encephalopathy (HE) in cirrhotic patients. We evaluated whether a diet and/or treatment with rifaximin or lactulose can reduce serum concentrations of BZDs in 18 cirrhotic patients without HE. Patients were given a standard diet for 7 days to keep the dietary intake of BZDs constant and were then randomized to a 7-day treatment with rifaximin 1,200 mg/day, lactulose 10-20 g three times daily, or placebo. Blood samples were collected at enrollment, at the end of the diet and drug treatment periods, and 7 days after the drug was stopped (follow-up). Serum concentrations of BZDs were measured by a radioligand binding technique after high-performance liquid chromatography extraction and purification and were expressed as diazepam equivalents (DE). No change in serum BZD concentrations was observed during the diet, while a statistically significant decrease from 105.6 +/- 66.5 to 63.5 +/- 49.5 pmol DE/ml was achieved in rifaximin-treated patients (p < 0.05) but not in patients treated with lactulose or placebo. During the followup, serum BZD concentrations returned to 104.5 +/- 74.0 pmol DE/ml in rifaximin-treated patients (p < 0.05 vs. end-treatment values), while no significant change was observed in the lactulose- and placebo-treated patients. These data indicate that control of bacterial flora with cyclic administration of rifaximin plays a pivotal role in avoiding increased plasma concentrations of BZDs, which represent a precipitating factor for HE inpatients with severe liver disease.

Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Results of a double-blind clinical study.

BACKGROUND: Chronic hepatic encephalopathy (HE) represents a frequent and serious complication of chronic liver disease. Aim of the study is to comparatively evaluate the effect of rifaximin, lactitol and their combination in treating chronic HE. METHODS: Forty out-patients (29 males, 11 females, mean age: 59 years, range 40-70), with viral liver cirrhosis and chronic HE (1st-2nd degree) were studied. HE was assessed by considering: mental state, asterixis, number connection test (NCT), arterial blood ammonia levels. Patients were randomly assigned to the following treatments: rifaximin (plus sorbitol as placebo) (group R); lactitol (group L); rifaximin plus lactitol (group RL). All treatments were continued for 15 days for 3 cycles, intervalled by 15 days of washout. RESULTS: The 3 treatments reduced HE, but with different efficacy: patients of group R and RL significantly (p<0.05) documented a faster improvement in HE degree, a higher percentage of patients which normalized mental state and NCT, a faster improvement of asterixis and a longer persistence of normal ammonia levels than patients of group L. CONCLUSIONS: Rifaximin in combination with lactitol or sorbitol represents an effective and safe treatment of chronic HE.

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms.

BACKGROUND: Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas-related symptoms with conflicting results. AIM: To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these symptoms. METHODS: Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double-blind, double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion. RESULTS: Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident. CONCLUSIONS: In patients with gas-related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.

Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth.

BACKGROUND: Bacterial overgrowth of the small intestine is a condition characterized by nutrient malabsorption due to an excessive number of bacteria in the lumen of the small intestine. Current treatment is based on empirical courses of broad spectrum antibiotics; few controlled data, with respect to the duration and choice of antibiotic drug, exist at present. The recent availability of rifaximin, a non-absorbable rifamycin derivative, highly effective against anaerobic bacteria, prompted us to carry out a randomized, double-blind controlled trial in order to compare its efficacy and tolerability to those of tetracycline, currently considered the first-choice drug. METHODS: In 21 patients affected by small intestinal bacterial overgrowth, fasting, peak and total H2 excretion after ingestion of 50 g glucose and severity of symptoms were evaluated before and after a 7-day course of rifaximin, 1200 mg/day (400 mg t.d.s.), or chlortetracycline, 1 g/day (333 mg t.d.s. ). RESULTS: Fasting, peak and total H2 excretion decreased significantly in the group of patients treated with rifaximin whereas chlortetracycline did not modify these parameters. The H2 breath test normalized in 70% of patients after rifaximin and in 27% of patients after chlortetracycline. The improvement in symptoms was significantly higher in patients treated with rifaximin. CONCLUSIONS: Rifaximin is a promising, easily-handled and safe drug for the short-term treatment of small intestinal bacterial overgrowth.

Effect of rifaximin on intestinal bacterial overgrowth in Crohn's disease as assessed by the H2-Glucose Breath Test.

UNLABELLED: The occurrence of intestinal bacterial overgrowth in patients with Crohn's Disease (CD) has been described and antimicrobial treatment has been shown to be effective in reversing this condition. However, the mechanisms underlying the efficacy of antimicrobial therapy are still only partially known. The aim of the present study was to evaluate the effect of a non-absorbable antibiotic (rifaximin) in comparison to placebo on bacterial overgrowth in patients with CD. METHODS: Fourteen patients with inactive CD of the ileum and bacterial overgrowth, as assessed by the hydrogen breath test, were blindly allocated to receive rifaximin (1200 mg/day) or placebo t.i.d. for one week. A hydrogen breath test, and clinical and biochemical parameters were further performed 14 days and 30 days after starting treatment. RESULTS: After 14 days, the hydrogen breath test proved to be negative in seven out of seven patients treated with rifaximin (p < 0.05), and in two out of seven in the placebo group (p = ns). After 30 days, the hydrogen breath test was positive in all patients of the rifaximin and placebo group, respectively. No changes in the CDAI score were documented in any patients. CONCLUSIONS: Short-term administration of rifaximin is effective in the therapy of bacterial overgrowth in patients with inactive CD of the ileum, thus suggesting that the control of luminal bacterial growth could be useful in the management of these patients. However, since we observed a decline with time in this positive effect, further studies are needed to identify the most appropriate therapeutic strategies.

Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease. AIMS: To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. PATIENTS AND METHODS: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture. RESULTS: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P < 0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance. CONCLUSIONS: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.

Intestinal bacterial overgrowth during chronic pancreatitis.

INTRODUCTION: The presence of an intestinal bacterial overgrowth (IBO) in patients with pancreatic insufficiency has been recently suggested to justify the worsening of their clinical conditions despite pancreatic enzyme supplementation. AIM: The purposes of this study were (a) to verify IBO frequency in patients with pancreatic insufficiency owing to chronic pancreatitis and (b) to evaluate the effect of chronic administration of a non-absorbable antibiotic, Rifaximin, in reducing IBO frequency and influencing the clinical picture of the disease. MATERIAL AND METHODS: Thirty-five patients with pancreatic insufficiency owing to chronic pancreatitis and 61 gastro-resected patients without pancreatic disease were studied. The presence of IBO was tested in both groups of patients using the hydrogen breath test with glucose. Chronic pancreatitis patients were subsequently treated with Rifaximin, 400 mg t.i.d for seven consecutive days each month for three months. RESULTS: A positive hydrogen breath test was present in 12 out of 35 (34%) chronic pancreatitis patients and in 13 out 61 (21%) controls (p < 0.002). In chronic pancreatitis patients an IBO was most likely to be present in the presence of a high ethanol intake, pancreatic microcalcifications, concomitant gallstones, diarrhoea and a history of gastric resection. In all patients with IBO, Rifaximin administration normalised the hydrogen breath test and reduced symptoms. CONCLUSIONS: IBO is frequent in patients with pancreatic insufficiency, particularly in those with a history of gastroduodenal surgery. Treatment with Rifaximin reduces IBO frequency and improves symptoms.

A randomized openly comparative study between rifaximin suspension versus rifaximin pills for the eradication of Helicobacter pylori.

BACKGROUND: It has been recently shown that Rifaximin, although given as a suspension, plus omeprazole, may be a promising antibiotic against Helicobacter pylori (H pylori) and worthy of further study. AIM: We have therefore evaluated Rifaximin suspension versus Rifaximin pills, in a randomly openly allocated fashion study, in H pylori positive patients. METHODS: Twenty patients with upper gastrointestinal symptoms (M/F: 13/7, age range 28-68; mean 49.6 yrs) were found to have H. pylori associated gastritis. They were allocated in an open randomized study to two different treatment groups for two weeks: (A) Rifaximin suspension 1800 mg three times a day plus Omeprazole 20 mg twice a day (n = 10), (B): Rifaximin pills 1800 mg three times a day plus Omeprazole twice a day (n = 10). Symptoms such as pirosis, bloating, epigastric pain and nausea were recorded by diary card and were evaluated before and four weeks after stopping treatment. Patients were assessed by endoscopy, histology and urease testing at entry and four weeks after stopping treatments. All the twenty patients were available four weeks after stopping treatment. RESULTS: A statistically significant improvement of the symptoms were found overall after Rifaximin treatments for pirosis, bloating, epigastric pain (p < 0.001 respectively). A significant difference in the symptom's score at the end of the two treatments were recorded between the two groups for bloating alone (p < 0.070). A different and major fall in the neutrophils, between the two treatments was observed with Rifaximin pills compared to Rifaximin suspension. The same observation was obtained according to the intensity of H. pylori reaching an eradication rate of 40% and 60% for Rifaximin suspension versus Rifaximin pills plus omeprazole respectively. In conclusion, these data suggest that Rifaximin pills may be an effective antibiotic against H pylori and worthy of further study.

Intestinal protozoa in HIV-infected patients: effect of rifaximin in Cryptosporidium parvum and Blastocystis hominis infections.

In HIV-1 infected patients severe enteritis and chronic diarrhea are often documented as a consequence of multiple opportunistic infections. We analyzed 48 HIV-1 positive patients for the presence of intestinal pathogenic protozoa. Patients with CD4 > or = 200/mm3 showed a higher prevalence of a single pathogenic protozoa than patients with CD4 < or =200/mm3, who showed the presence of multiple protozoal infections. Patients who proved positive for only a single protozoa, Cryptosporidium or Blastocystis, were also positive, by stool culture, for the presence of Proteus mirabilis (3 samples), Citrobacter freundii (3 samples), Escherichia coli (one sample) or Enterobacter cloacae (one sample). Treatment with rifaximin (600 mg, 3 times a day, for 14 days) was efficacious in resolving the clinical symptoms and clearing protozoan infections in HIV-1 infected patients with CD4 > or = 200/mm3, who presented enteric and systemic symptoms due to Criptosporidium or Blastocystis associated with enteropathogenic bacteria.

Review--antibiotic treatment in inflammatory bowel disease: rifaximin, a new possible approach.

The etiology of inflammatory disease is still unknown, but a body of evidence from clinical and experimental observation indicates a role for intestinal microflora in the pathogenesis of this disease. Reduction of microflora using antibiotics, bowel rest and fecal diversion decreases activity in Crohn's disease and in ulcerative colitis. Several trials have been carried out on the use of antibiotic treatment in patients with active ulcerative colitis with contrasting results. A number of trials have been carried out using Rifaximin, a non-absorbable broad-spectrum antibiotic, confirming the absence of systemic bioavalaibility of the drug even when administered at very high doses and for prolonged periods. It may therefore be useful in treatment of ulcerative colitis and pouchitis, since its absorption through inflamed mucosa is negligible, it maintains a topical action without systemic effects and the lack of resistant bacterial strains may allow prolonged and repeated treatments.

Rifaximin and Helicobacter pylori eradication.

In this study, we tested the effectiveness of Rifaximin, a surface antibiotic which is not absorbed when given orally, in the eradication of Helicobacter pylori (HP). The drug was combined in triple therapy either with Amoxicillin and Omeprazole or with Erythromycin-ethylsuccinate and Omeprazole. Twenty-three patients complaining of dyspeptic symptoms and gastric infection due to HP were evaluated. The patients were randomly given one of the following therapeutic protocols: Rifaximin susp. 600 mg/day x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Amoxicillin tab. 1 g x 2/day (at least two hours after meals: 10:00 am, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol A) and Rifaximin susp. 600 mg/day x 3/day and Erythromycin-ethylsuccinate tab. 600 mg x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol B). Both therapeutic protocols were prescribed for two weeks. At least one month after the end of the treatment the patients were controlled to ascertain eradication of the infection. The follow-up carried out after treatment showed that HP infection was eradicated in 6 of 10 patients in the first group (protocol A) and in 1 of 10 in the second group (protocol B). These patients were HP-negative in all the tests performed: histological, CP-TEST, culture test. The data collected showed a reasonable level of effectiveness of the protocol using the combination Rifaximin-Amoxicillin and Omeprazole. However, they do not differ from the reported data in the literature which show a similar effectiveness of the combination Omeprazole-Amoxicillin at the same doses. Different formulations that makes it possible for the drug to reach these "protected areas" would probably be more effective.

Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis.

Benzodiazepine-like compounds are present in trace amounts in the blood of normal subjects and increase in liver cirrhotic patients with or without encephalopathy. Their increased presence may, however, represent an occasional precipitating factor of hepatic encephalopathy. The source of these compounds is still unknown, but they are constituents of our diet since benzodiazepine receptor ligands have been described in plants, vegetables and in animals. They may also be synthesized, at least in part, by intestinal bacterial flora. In this article we report that the level of these compounds in the blood decreased by 40% after therapy with rifaximin, which reduces the aerobic and anaerobic intestinal bacterial flora. This observation indicates that intestinal bacterial flora is involved in the production of these compounds and that repeated short-term medications with this non-absorbable antibiotic may be useful in reducing the levels of benzodiazepine-like compounds in patients with liver cirrhosis.

Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial.

The aim of this study was to evaluate the efficacy and tolerability of rifaximin, a non-absorbable intestinal antibiotic, in comparison to neomycin in the short- and long-term treatment of hepatic encephalopathy (HE). Forty-nine patients with a definite diagnosis of cirrhosis were included in this double-blind, randomised, controlled trial. Patients were randomly assigned to one of the following treatments: (1) rifaximin 400 mg three times daily; (2) neomycin 1 g three times daily. Both drugs were administrated orally as tablets during 14 consecutive days each month, for a period of six months. The neuropsychiatric signs and blood ammonia levels were examined before starting the treatment, and every 30 days, until the final assessment. In all patients a progressive and important reduction in HE grade was observed, and no statistically significant difference between the two treatments was detected. In both groups the disturbances in speech, memory, behaviour and mood, gait, asterixis, writing, and serial subtraction of 7 s and five-pointed star tests all showed the highest proportion of improvement. During the study blood ammonia levels decreased in both the rifaximin and in the neomycin groups, and again no statistically significant difference was found between groups. Our findings confirm, therefore, the usefulness of rifaximin in the treatment of HE, supporting its use as a first-choice antibiotic, particularly in patients intolerant to neomycin or with impaired renal function.

Rifaximin in the treatment of chronic hepatic encephalopathy.

A study was performed to assess the efficacy and tolerability of rifaximin in the treatment of encephalopathy during cirrhosis of the liver. Fifty-five patients suffering from grade 1, 2 and 3 portosystemic encephalopathy, with a mean age of 58.9 years (range 30 to 86 years) were evaluated. The patients were treated for 15 consecutive days with rifaximin, an antibiotic which is not absorbed by the intestinal wall, at a dosage of 1200 mg/day in association with sufficient lactulose to induce 2 or 3 evacuations per day. Combined use of the 2 drugs proved an efficient means of controlling the majority of signs and symptoms. After just a few days, an improvement in the signs of encephalopathy was noted in all patients. The treatment was well tolerated and the patients completed the trial without any drug-related side-effects. The results of our trial, although in the context of an open assessment, confirm the clinical efficacy of rifaximin in association with a non-absorbable disaccharide such as lactulose. The 2 compounds have a synergetic effect in reducing ammonia-producing flora. Its efficacy and good tolerability make rifaximin a valid alternative to the use of aminoglycoside antibiotics associated with disaccharides in the treatment of patients with liver disease, particularly in the case of prolonged therapy.

The natural history of diverticular disease of the colon: a role for antibiotics in preventing complications? A retrospective study.

Medical and surgical treatment of diverticular disease has to be set against a background of incomplete knowledge of the natural history and geographical differences of the disease, and difficulties in its definition and classification. This clinical retrospective study was performed to answer the following questions: 1) what was the clinical course after an episode of acute diverticulitis, obliging to an hospital admission? 2) what was the role of cyclic course of antibiotics, if any, in reducing the risk of complications? We examined all admissions to the surgical ward from 1967 to 1991 for a complication of diverticular disease: we looked for occlusion, perforation, fistula, or bleeding. Patients not operated with diverticular disease have been divided in 2 groups, that is patients with a medical prescription at the end of hospital period, and patients admitted without a drug prescription. All patients have been prescribed bulk agents. The medical prescription included monthly cycles of 1 week of oral antibiotics (Neomycin associated with Bacitracin, Paromomycin, or 1989 Rifaximin). We looked for the natural history of the disease in the 2 groups (the "drug" group and the "no drug" group) after the first admission, that is the development of new complications of the diverticular disease and the reason for readmissions, calculating the Absolute Risk Reduction (the difference in event rates between the treatment and control groups) and the Relative Risk Reduction (the difference in event rates between the treated and control groups, divided by the event rate in the control groups). The total number of admitted patients in the period 1967-1991 was 505. A statistically significant trend in favour of a risk reduction of new admissions in the group given antibiotics seems evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test.

To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10 g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400 mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p < 0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r = 0.49, p < 0.01) and after rifaximin (r = 0.58, p < 0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antihypertensive action of nicardipine retard in 24 hours and its effect on stress]. / Azione antiipertensiva della Nicardipina Retard nelle 24 ore e suo comportamento nello stress.

Thirty-six patients (17 males and 19 females), aged between 40 and 70 years old (mean age 55.9), suffering from slight or moderate arterial hypertension, were monitored for four weeks after 14 days of placebo treatment. In a double-blind and random study 24 patients were treated with Nicardipine Retard (40 mg twice a day) whereas a further 12 received placebo twice a day. Sphigomanometric controls carried out after two and four weeks showed a significant reduction in arterial pressure only in those patients receiving active treatment. 24-hour out-patient monitoring of arterial pressure, carried out using Spacelabs 5300, showed a reduction in both systolic and diastolic arterial pressure throughout the day in subjects treated with calcium-antagonists compared to the placebo group. The normal physiological 24-hour trend of arterial pressure was always taken into account. The pressure response to a cold pressor test, mental arithmetic test, isometric and dynamic effort tests, measuring using a cycloergometer, was not modified by anti-hypertensive treatment, thus confirming the preservation of normal physiological behaviour during daily activities. There was no significant change in heart rate and the drug was well tolerated.

[Slow-release nicardipine in the treatment of arterial hypertension: comparative study vs. an ACE inhibitor]. / Nicardipina a lento rilascio nel trattamento dell'ipertensione arteriosa: studio comparativo verso un aceinibitore.

The anti-hypertensive activity and influence on some forms of stress of slow-release Nicardipoine and Captopril were compared using a randomized 2:1 protocol. Thirty-six patients, mean age 55.9 years, suffering from slight or moderate arterial hypertension were treated with either 40 mg of Nicardipine retard twice a day (b.i.d.), or Captopril in a dose of 25 mg (b.i.d.) for 8 weeks. A significant reduction was observed in arterial pressure, both in orthostatism and clinostatism, following both treatments in comparison to the placebo period, but the group treated with slow-release Nicardipine showed a greater and statistically significant reduction in arterial pressure. No significant change in heart rate was reported using either drug. Non-invasive out-patient monitoring of arterial pressure, performed using Spacelabs 5300, showed a significant reduction in arterial pressure using both drugs and the conservation of the normal circadian rhythm of arterial pressure. The pressure response to the cold pressor test (CPT), mental arithmetic test (MAS), and to dynamic and isometric effort was positive with both drugs, thus revealing a degree of protection offered by treatment using these two substances. In overall terms, the two drugs were well tolerated.