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Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal-strength antacid.

This study tested the hypothesis that (alginic) acid may have a preferential effect on reflux in the upright position. We evaluated the effect of a compound containing alginic acid plus antacid (extra-strength Gaviscon) versus active control antacid with equal acid-neutralizing capacity on intraesophageal acid exposure following a high-fat meal (61% fat: sausage, egg, and biscuit). In random sequence, each of the 10 volunteers received either alginic acid-antacid or control antacid immediately following and 1, 2, and 3 hr after the meal. The sequence was repeated for both test drugs in the supine and upright positions with constant pH monitoring. Alginic acid-antacid significantly decreased postprandial reflux in the upright position compared to an equal amount of antacid. This effect did not occur in the supine position. These findings support the hypothesis that alginic acid is primarily effective in the upright position and the clinical observations of the effectiveness of alginic acid on daytime reflux symptoms.

Alginates↗

Palatability of 14 over-the-counter antacids.

Although a number of differently flavored antacids have been introduced recently, no blinded comparative palatability evaluations have been conducted since 1977. A comparative, randomized, single-blind evaluation of over-the-counter aluminum and magnesium antacid suspensions was conducted to determine their relative palatability. Thirty healthy volunteers were asked to evaluate 14 antacids for smell, taste, texture, and aftertaste. The study found a statistically significant difference in all rated characteristics of antacids. Mylanta Cherry Creme (score 24.4 out of possible 36) and Mylanta Double Strength Cool Mint Creme (score 24.2) were ranked highest in overall palatability; Riopan Plus 2 (score 18.7) and Di-Gel Lemon Orange (score 18.0) were ranked lowest. The study concluded that the palatability of various antacid suspensions differs markedly and should be considered when selecting an antacid product.

Adult↗

Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization.

Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2-blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress-ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers.

Antacids↗

Antacid pulmonary aspiration in the dog.

The amount of damage resulting from pulmonary aspiration of gastric contents is determined primarily by the acidity of the aspirate. Thus, it has been recommended that the pH of stomach contents of pregnant women be increased by the oral administration of antacids prior to anesthesia for delivery. This study was done to investigate the effects of antacid aspiration in dogs and compare these effects with those obtained by trials of aspiration of acid, saline solution, and alkaline saline solution. Mean PaO2 of the saline-treated group had decreased from 81 to 60 torr at 10 min, while that of the alkaline saline-treated group had decreased from 83 to 58 torr. Fractional intrapulmonary physiologic shunt (Qs/Qt) increased in these two groups, from 15 to 34 and from 16 to 42 per cent, respectively. The Qs/Qt had returned to control values in both groups by four hours, and the PaO2 had returned to control values by 24 hours. By contrast, the acid- and antacid-treated groups had decreases in PaO2 values from 77 to 34 torr and from 84 to 46 torr, respectively. Neither group had a return of PaO2 to pre-aspiration level by 24 hours. Likewise, the Qs/Qt increased significantly more in these two groups: 14 to 66 per cent in the acid-treated group and 13 to 47 per cent in the antacid-treated group. These changes persisted throughout four hours. The saline and alkaline saline aspirates produced little histologic damage. The acid aspirate produced hemorrhage, exudates, and edema. However, these changes were no longer present a month later. The antacid aspirate produced a marked bronchopneumonia that was still present as a chronic inflammatory reaction after a month. These findings indicate that antacids can cause pulmonary damage when aspirated.

Animals↗

Antacid control of complications from acute gastroduodenal disease after burns.

To determine the effectiveness of hydrogen ion neutralization in preventing the clinical complications (hemmorrhage and perforation) of acute gastroduodenal disease after thermal injury, 48 patients with burns of greater than 35% total body surface were evaluated within 72 hours after injury. In a prospective, randomized fashion, patients were chosen to receive antacid or no-antacid therapy. An established lithiumflux technique was utilized to determine the integrity of the gastric mucosal barrier (GMB) before group selection. Only one of the 24 patients receiving antacid developed significant upper gastrointestinal bleeding; however, seven of 24 patients receiving no antacid experienced hemorrhage and gastric ulcer perforation (p less than 0.02). None of seven patients with GMB disruption who received antacid developed a clinical complication; however, six of 15 patients with GMB disruption receiving no antacid experienced clinical complications (p less than 0.05). Neutralization of gastric acid offers protection against the development of clinically significant ulcer complications in the burn patient.

Acute Disease↗

Effect of antacids on phenytoin bioavailability.

Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally. Each subject received phenytoin alone on two separate occasions and phenytoin plus each of the three antacids on three other occasions. Each antacid was administered as 160 mEq at 1 and 3 hr after each meal and at bedtime on the day phenytoin was given. The mean area under the curve (AUC) was significantly decreased by AMH (p less than 0.005) and CC (p less than 0.05). AHMT had a similar trend but did not reach statistical significance (p = 0.1). Large inter- and intrasubject variability in AUC was observed when phenytoin was administered alone. In two subjects, cumulative urinary 5-(4-hydroxyphenyl)-5-phenylhydantoin at 72 hr (HPPH72) was determined. The amount of HPPH recovered had similar trends as the AUC with antacid treatments but not the same magnitude. In this study, antacids altered not only the extent of absorption but also appeared to alter the rate of absorption. Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin.

Adult↗

Prescribing of antacids and ulcer-healing drugs in primary care in the north of England.

BACKGROUND: This study describes the pharmaco-epidemiology of ulcer-healing therapies in primary care in the north of England. METHODS: Anonymous patient-specific prescribing data were extracted from computerized general practice records for 41 practices. Prescribing prevalences were determined according to patient age, gender and recorded prescription indication, for both antacids and H2-receptor antagonists or omeprazole. RESULTS: During the year of the study, antacids were prescribed for 3.9% of the study population, and H2-receptor antagonists or omeprazole for 3.7%. Rates increased with age, peaking at 99 (antacids) and 87 (H2-receptor antagonists) per 1000 population aged 65-84 years. Antacid prescribing rates for women were over twice those for men amongst those aged 15-34 years. For H2-receptor antagonists, rates were higher in men than women, with the excess attributable to prescribing for ulcer indications, although at all ages prescribing for oesophagitis was more prevalent among women. Of the patients prescribed H2-receptor antagonists or omeprazole, 45% (accounting for 51% of prescription items) had indications which included peptic ulcer or oesophagitis, 42% had gastritis or dyspepsia only (35% items), and in 13% no peptic indication was recorded. For each of antacids and H2-receptor antagonists, the practices had similar prescribing profiles according to patient age and gender, but their absolute levels differed up to two-fold. CONCLUSIONS: Prescribing of antacids and ulcer-healing drugs varies systematically with patient age and gender. Consequently, evaluation of crude prescribing rates, without reference to patient demography, is unreliable as a guide to levels of usage. In general practice, H2-receptor antagonists and omeprazole appear to be over-prescribed for minor indications.

Adolescent↗

Effect of food on antacid neutralizing capacity in man.

In order to estimate their in-vivo reactivity two antacids of equal theoretical neutralizing capacity (approximately 3.9 mol/l at pH 3.5) but of different chemical composition were employed as intragastric titrant (pH 3.5) following a liquid protein meal (oxo) in two groups of five volunteers each. The two antacids chosen (alucol and Camalox) contain different amounts of aluminium hydroxide, magnesium hydroxide and Camalox in addition contains calcium carbonate. The intragastric consumption of these two antacids was much higher than their respective theoretically available neutralizing capacity (Alucol 3.9 times, Camalox 2.4 times). In-vitro studies demonstrated that interaction with oxo reduced the neutralizing capacity of the two antacids at pH 3.5 from 3.9 mol/l to 1.7 mol/l (Alucol) and 2.5 mol/l (Camalox). This potency loss was related to the aluminium hydroxide content of the two antacids. This study indicates that the neutralizing capacity of antacids is not predictable from their reactivity in aqueous solution and is markedly reduced by protein-containing foods.

Adult↗

Aluminium absorption and antacid therapy in infancy.

The aim of this study was to determine whether infants absorb aluminium from antacid therapy. The study was conducted at Torrens House, a service provided by Child and Adolescent Health Services (CAFHS) for feeding and settling problems. Over an 11 week period, all patients receiving antacid therapy were studied. Patients not receiving antacids but of similar age acted as controls. Plasma and urine levels of aluminium were measured. The 15 infants receiving antacids had higher aluminium levels than the 17 controls (plasma 3.3 +/- 2.2 mumol/L vs 1.5 +/- 1.5 mumol/L, P less than 0.01; urine 25.1 +/- 27.6 mumol/L vs 1.1 +/- 1.8 mumol/L, P less than 0.004). The response was variable with 50% of infants receiving antacids recording plasma aluminium levels previously associated with toxicity in patients with renal failure after chronic exposure to aluminium. We conclude that infants absorb aluminium from antacids and suggest that patients receiving have their plasma levels monitored to identify those at possible risk of toxicity.

Aluminum↗

Buffering effect of antacids in the mouth--a new treatment of dental erosion?

Antacids are drugs of choice in the treatment of reflux esophagitis and peptic ulcer disease, where acid regurgitation may cause dental erosion. Since there are no specific preventive measures or effective treatment for erosions, the present study was made to assess whether the keeping of antacids in the mouth before swallowing would be beneficial with regard to their effect on mouth pH, after acidic challenge. Five healthy subjects formed the test panel. After measuring the acid binding capacity of all the antacid preparations in the Finnish market, the two most effective were selected for testing, one in emulsion form (Novaluzid), the other a tablet (Link). Acid regurgitation was mimicked by consuming a low-pH (3.2) drink immediately before the antacid. Control series were made with the acidic drink only. Both the antacids were found to counteract totally the pH fall caused by the drink, when measured as changes in the tongue surface pH. The Novaluzid preparation was more effective than the Link preparation but the difference was not significant. It may be anticipated that patients suffering from acid regurgitations would benefit if they are counseled to keep their antacids in the mouth for a while before swallowing.

Acids↗

Biopharmaceutical properties of liquid and tablet antacids: in vivo studies using the intragastric pH-measurement technique.

Three types of liquid and tablet antacids have been studied in vitro and in vivo: aluminium hydroxide, aluminium hydroxide-magnesium carbonate and hydrotalcite. The effects on gastric pH of antacid suspensions and antacid chewing tablets having identical active ingredients have been studied in 36 volunteers, the sequence of both forms of administration being randomized. Gastric acid secretion was continuously stimulated during the experiment by a pentagastrin infusion. Antacid chewing tablets gave inferior results when compared with the same antacid in liquid. Antacid suspensions are therefore preferred in the treatment of acid-peptic disease.

Antacids↗

Effects of magnesium-aluminum hydroxide and calcium carbonate antacids on bioavailability of ofloxacin.

The effects of 15- and 5-ml doses of magnesium-aluminum hydroxide (MAH) and calcium carbonate (CC) antacids, respectively, on the bioavailability of ofloxacin after single oral 400-mg doses of ofloxacin were investigated in a 32-subject, randomized, crossover, open-label study. On four separate occasions, subjects received ofloxacin alone or antacid 24 h before, 2 h before, or 2 h after ofloxacin administration (n = 16 for each antacid). CC administration had no significant effect on the rate and extent of ofloxacin absorption regardless of the timing of antacid administration. A small but significant negative effect of MAH administration 2 h before ofloxacin administration was noted as evidenced by area under the curve and peak concentration in plasma data. Simultaneous administration of ofloxacin with either antacid was not investigated in this study. It appears that MAH and CC antacids in the doses used in this study generally do not interfere in a clinically significant manner with the bioavailability of ofloxacin, provided that an interval of at least 2 h separates the administration of these products.

Adolescent↗

Influence of antacid and ranitidine on the pharmacokinetics of oral cefetamet pivoxil.

The purpose of this investigation was to assess the influence that treatment with antacid and ranitidine had on the pharmacokinetics of oral cefetamet pivoxil in 18 healthy male volunteers. Each subject received, in an open-labeled, randomized, three-way crossover design, a single oral dose of 1,000 mg (two tablets) of cefetamet pivoxil 10 min after a standard breakfast during each of the following treatments: treatment A, control period; treatment B, antacid (80 ml of suspension; Maalox 70) administered on the evening before cefetamet pivoxil dosing (-12.5 h) and again 2 h before and 2 h after a standard breakfast; treatment C, ranitidine (150 mg) administered twice a day for 4 days and again 1 h and 10 min prior to cefetamet pivoxil dosing. Plasma and urine samples were collected over a 24-h period following cefetamet pivoxil administration. Cefetamet was analyzed by high-performance liquid chromatography. Oral bioavailability parameters (area under the concentration-time curve from 0 to 12 h, area under the concentration-time curve from 0 h to infinity, time to maximum concentration of drug in plasma, and maximum concentration of drug in plasma) were obtained by noncompartmental techniques. The results showed that none of these bioavailability parameters was significantly (P greater than 0.05) affected by antacid or rantidine coadministration. A compartmental analysis showed no significant differences. In addition, the terminal elimination half-life and the fraction of cefetamet excreted unchanged in the urine was also not significantly (P greater than 0.05) affected by antacid or ranitidine exposure. Relatively wide intrasubject variability was observed for time to maximum concentration of drug in plasma and terminal elimination half-life in several of the 18 subjects studied. Although these irregularities did not appear to be strongly associated with a particular treatment, they increased in subjects in both the antacid and H2-receptor antagonist treatment groups compared with those in subjects in the control treatment group. We conclude that antacid and ranitidine treatment likely does not alter the bioavailability of oral cefetamet pivoxil.

Administration, Oral↗

Effects of magnesium-aluminum hydroxide antacid on absorption of rufloxacin.

The present study was designed to determine the effects of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (30 ml of Maalox) on the oral bioavailability of rufloxacin (400 mg). Rufloxacin was administered orally to 12 healthy volunteers according to a randomized, balanced, crossover design. Three treatments were administered to each subject, with a 10-day washout period between treatments; the treatments included rufloxacin alone, rufloxacin taken 5 min after antacid, and rufloxacin taken 4 h before antacid. Administration of antacid within 5 min before the administration of rufloxacin resulted in a substantial decrease in rufloxacin absorption, with a mean percent relative bioavailability compared with control values of 64% (range, 42 to 77%). Administration of antacid 4 h after the administration of rufloxacin slightly affected the absorption of the quinolone (mean relative bioavailability, 87%; range, 51 to 110%). Antacids that contain magnesium and aluminum salts reduce the absorption of rufloxacin. The extent of this interaction depends on the time that elapses between administration of the two drugs.

Administration, Oral↗

Effect of oral antacids on disposition of intravenous enoxacin.

The effect of an intensive aluminum-magnesium hydroxide antacid regimen (Maalox TC) on the disposition of intravenous enoxacin was studied in six male and six female volunteers. A single 400-mg dose of enoxacin was administered intravenously over 30 min on two occasions separated by a 1-week washout period. Thirty milliliters of Maalox TC was administered at -8, -2.5, -0.5, 1.5, 3.5, 5.5, 7.5, 9.5, 11.5, 13.5, and 15.5 h relative to the start of one enoxacin infusion. The enoxacin dose in which antacid was coadministered was randomly selected. Fourteen plasma samples were collected over 24 h, and urine was collected in two divided intervals over 48 h. Enoxacin concentrations in plasma and urine samples were determined by high-performance liquid chromatographic assays. The intensive antacid regimen did not change the total clearance (P = 0.058) or steady-state volume of distribution (P = 0.516) for enoxacin. However, the nonrenal clearance and half-life were significantly altered (P < 0.05). The mean nonrenal clearance increased from 13.27 +/- 3.33 to 15.68 +/- 2.35 liters/h (18.2%) following the antacid regimen. This effect of antacid is unlikely to be of clinical significance. Enoxacin may be administered intravenously, but not orally, without regard to antacid treatment.

Administration, Oral↗

Effect of an antacid containing magnesium and aluminum on absorption, metabolism, and mechanism of renal elimination of pefloxacin in humans.

The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were investigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple doses of the antacid. The concentrations of pefloxacin and its metabolites in plasma and urine were determined by high-performance liquid chromatography assays. We found that coadministration of magnesium and aluminum hydroxide caused a decrease of levels of pefloxacin in plasma and urine. The area under the plasma concentration-time curve decreased significantly (P < 0.001), suggesting impaired absorption of pefloxacin from the gastrointestinal tract. The relative bioavailability of pefloxacin after the antacid treatment was 44.4% +/- 23.8%, compared with that after a single administration. The underlying mechanism of this drug interaction is the formation of chelate complexes and probably also physical adsorption to the aluminum hydroxide gel. The metabolism of pefloxacin was not altered by the antacid treatment. Renal clearance was found to depend on urinary pH. Terminal half-life was significantly shorter after the antacid treatment, probably because of an increase in nonrenal clearance. In conclusion, pefloxacin should be given at least 2 h before the antacid to ensure sufficient therapeutic efficacy of the quinolone.

Adult↗

Pharmacokinetics of ethionamide administered under fasting conditions or with orange juice, food, or antacids.

This study was conducted in order to (i) determine the effect of food, orange juice, or antacids on the absorption of a single oral 500-mg dose of ethionamide (ETA) in healthy volunteers, including an assessment of bioequivalence, and (ii) determine ETA population pharmacokinetic (PK) parameters. The pharmacokinetics of ETA in serum was determined for 12 healthy males and females in a randomized, four-period crossover study. Volunteers received single 500-mg doses of ETA either on an empty stomach (reference) or with food, orange juice, or antacids. Serum samples were collected for 48 h and assayed by high-performance liquid chromatography. Data were analyzed by noncompartmental and population methods. Mean test/reference ratios and 90% confidence intervals were determined. No statistically significant differences were seen in the maximum concentration of ETA (C(max)), time to maximum concentration (T(max)), or area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) between the four treatments (P > 0.05 by analysis of variance). The least-squares mean ratios (with confidence intervals in parentheses) for C(max) were 105% (81.2 to 135%) after orange juice, 94% (72.8 to 121%) after food, and 88% (68.4 to 114%) after antacids. The least-squares mean ratios (with confidence intervals is in parentheses) for AUC(0-infinity) were 91% (72.7 to 115%) after orange juice, 96% (76.4 to 121%) after food, and 95% (75.5 to 120%) after antacids. The mean T(max) was slightly prolonged following antacid or food administration (2.3 to 2.6 h) compared to administration on an empty stomach or with juice (1.7 to 1.9 h). The median population PK parameters were as follows: K(a) = 0.37 to 0.48 h(-1), V/F = 2.0 to 2.8 liters/kg, CL/F = 56.5 to 72.2 liters/h, and terminal half-life = 1.7 to 2.1 h, where K(a) is the absorption rate constant, V is the volume of distribution, and CL is clearance. The PK behavior of ETA was not significantly modified by the different conditions studied. Mean ratios for AUC ranged from 0.91 to 0.96 for the orange juice, food, and antacid treatments, indicating a minimal effect on relative bioavailability. ETA can, therefore, be administered with food if tolerance is an issue.

Adolescent↗

Antacids and cimetidine treatment for gastro-oesophageal reflux and peptic oesophagitis.

Thirty three children aged 2 to 42 months (mean 9 months) with gastro-oesophageal reflux and peptic oesophagitis took part in a treatment trial comparing cimetidine (20 mg/kg/day) with an intensive regimen of antacids (Maalox, 700 mmol (mEq)/1 X 73 m2/day). All children were evaluated clinically and by radiology, acid reflux test, and endoscopy. After 12 weeks of treatment all were again evaluated clinically, by pH measurement, and endoscopy. Twenty nine children, 15 on antacid and 14 on cimetidine, completed the trial. Eight patients on antacid and seven on cimetidine were cured; five on antacid and six on cimetidine improved; and two patients on antacid and one on cimetidine underwent surgery. Both groups of children showed a statistically significant reduction in the score of clinical, pH, and endoscopic variables after treatment. Lower oesophageal sphincter pressure before treatment did not correlate significantly with the final total score. Antacids in large quantities are as effective as cimetidine in medical treatment of gastro-oesophageal reflux and peptic oesophagitis.

Aluminum Hydroxide↗