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The bio-availability of beta-acetyldigoxine alone and combined with aluminum hydroxide and magnesium hydroxide (Alucol).

The bio-availability of Novodigal (beta-acetyldigoxine) alone and applied together with Alucol (aluminum hydroxide, magnesium hydroxide) was studied in six healthy probands. Bio-availability parameters were calculated from the areas under the plasma concentration curves and from the comparison of the blood levels after absorption during steady state. There was no significant difference between the bio-availability of beta-acetyldigoxine alone and that of the combination with Alucol. Thus, beta-acetyldigoxine combined with antacids of the aluminum hydroxide and magnesium hydroxide type can be applied in the same dosage as usual since no decrease of effect has to be apprehended.

Adult

Enhancement of absorption and effect of glipizide by magnesium hydroxide.

The effects of magnesium hydroxide on the pharmacokinetics and pharmacodynamics of glipizide were studied in eight healthy volunteers in a randomized crossover trial. After an overnight fast, 5 mg glipizide was given with either 150 ml water or water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the areas under the plasma glipizide concentration-time curves (AUC) from 0 to 1/2 hour and from 0 to 1 hour by 180% (p less than 0.05) and 69% (p less than 0.05), respectively. The peak plasma concentration, time to peak, total AUC, elimination half-life, and mean residence time of glipizide remained unchanged. The incremental plasma insulin area from 0 to 1/2 hour increased by 85% (p less than 0.05), and the time to maximal insulin response was reduced (p less than 0.05) during the magnesium hydroxide phase. The corresponding decremental plasma glucose area increased fourfold (p less than 0.05), and the maximal glucose decrease was 35% greater (p less than 0.05) than during the control phase. We conclude that the concomitant ingestion of magnesium hydroxide and glipizide may result in accelerated absorption of glipizide and increased early insulin and glucose responses.

Adult

Effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide.

The effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide was examined in a total of 32 healthy volunteers in two separate, randomized parallel-group studies, with 16 subjects in each study. After an overnight fast, the first group of 8 volunteers ingested 500 mg tolbutamide or 250 mg chlorpropamide with 150 ml water, and the second group the same doses of the active drugs with 150 ml water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the area under the plasma tolbutamide concentration-time curve (AUC) from 0 to 1 h and from 0 to 2 h by 5-fold and 2.5-fold, respectively. The peak plasma concentration, peak time and total AUC were not significantly altered. The incremental insulin area and the decremental glucose area from 0 to 1.5 h were significantly larger in the magnesium hydroxide group than in the controls. The maximum insulin response to tolbutamide was increased fourfold by coadministration of magnesium hydroxide, and it occurred about 1 h earlier than in the control group. In addition, the maximum fall in plasma glucose concentration was attained about 1 h earlier in the antacid group. A tendency to an increased rate of chlorpropamide absorption was observed after magnesium hydroxide, but it did not appear to affect the insulin and glucose responses to chlorpropamide. It is concluded that magnesium hydroxide increased the early bioavailability of tolbutamide, resulting in enhanced insulin and glucose responses. A tendency toward accelerated chlorpropamide absorption by magnesium hydroxide was also observed, but the efficacy of chlorpropamide was unaffected.

Adult

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

1. The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2. A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after the ingestion of a micronised (1.75 mg, seven subjects) or a non-micronised (2.5 mg, six subjects) preparation of glibenclamide. Plasma concentrations of glibenclamide, insulin and glucose were measured. 3. Magnesium hydroxide accelerated (P less than 0.05) the absorption of glibenclamide from the micronised preparation to a small extent but the extent of absorption and the insulin and glucose responses were unaltered. 4. Coadministration of magnesium hydroxide with the non-micronised glibenclamide preparation increased the area under the plasma glibenclamide concentration-time curve from 0 to 3 h, five-fold (P less than 0.05), the total area three-fold (P less than 0.05) and the peak drug concentration three-fold (P less than 0.05). The incremental insulin area from 0 to 3 h was increased 35-fold (P less than 0.05) and the maximum insulin response 10-fold (P less than 0.05) by magnesium hydroxide. 5. Concomitant ingestion of magnesium hydroxide and non-micronised glibenclamide may greatly enhance the absorption and efficacy of glibenclamide. The absorption of micronised glibenclamide appears to be only slightly influenced by magnesium hydroxide.

Adult

The effect of magnesium hydroxide on the oral absorption of ibuprofen, ketoprofen and diclofenac.

1. The effect of magnesium hydroxide on the oral absorption of ibuprofen, ketoprofen and diclofenac was investigated in two randomized cross-over studies, both consisting of two phases. 2. Single doses of magnesium hydroxide (850 mg) or of water (150 ml) only were given to six healthy volunteers immediately after the ingestion of ibuprofen (400 mg, Study 1), ketoprofen (50 mg, Study 2) or diclofenac (50 mg, Study 2). Plasma drug concentrations were measured up to 24 h. 3. Magnesium hydroxide increased the area under the plasma ibuprofen concentration-time curve between 0 and 1 h by 65% (P less than 0.05) and the peak concentration of ibuprofen in plasma by 31% (P less than 0.01). The time to peak was shortened by about 0.5 h. The extent of bioavailability of ibuprofen was not increased by magnesium hydroxide. 4. Neither the rate nor the extent of absorption of ketoprofen or diclofenac was changed significantly by magnesium hydroxide. 5. When rapid onset of the analgesic effect of ibuprofen is required, concomitant ingestion of an antacid, which contains magnesium hydroxide without aluminium, is recommended.

Adult

Effect of interaction of aluminum hydroxycarbonate gel and magnesium hydroxide gel on acid neutralization.

Acid neutralization by mixtures of aluminum hydroxycarbonate gel and magnesium hydroxide gel differs from the sum of the acid neutralization of each gel. Acid neutralization by magnesium hydroxide gel in the mixture is not observed until after a substantial portion of the aluminum hydroxycarbonate gel has reacted with acid, even though magnesium hydroxide gel is the faster reacting of the two gels. It is hypothesized that amorphous aluminum hydroxycarbonate forms a coating on the crystalline magnesium hydroxide particles due to electrostatic attraction. This coating prevents protons from reaching the highly reactive magnesium hydroxide until the coating is dissolved by the acid neutralization of aluminum hydroxycarbonate.

Acids

Effect of magnesium hydroxide on methylazoxymethanol acetate-induced epithelial proliferation in the large bowels of rats.

The effect of magnesium hydroxide on the epithelial proliferation of the large bowel was examined using rats given methylazoxymethanol (MAM) acetate. Dietary administration of magnesium hydroxide at 250, 500, 1000 or 2000 ppm. for 1, 3 or 5 weeks did not influence the cell cycle of the cryptal cells of the large bowel. However, the exposure to magnesium hydroxide under these conditions lowered the bromodeoxyuridine labeling index of the cells of the large bowel of the rats which had been initiated by MAM acetate (25 mg/kg, 3 times). The decrease in labeling index was more apparent in the proximal segment than in the distal segment. Such an inhibitory effect on the DNA synthesis of the epithelial cells by magnesium hydroxide may be related to the suppressive action of the trace element on the carcinogen-induced large bowel carcinogenesis.

Animals

[Effects of the administration of magnesium hydroxide on gastric acidity in health volunteers].

Antacids are often the first therapeutic approach in patients with pyrosis. We carried-out a study on 8 healthy volunteers who underwent a 24 hour gastric pH-metry to assess the real efficacy of magnesium hydroxide administration on gastric acidity. Magnesium hydroxide was alternatively administered at different dosages (400 mg or 800 mg) in the population studied. Our results showed a mild and non reproducible response to lower dose, but, on the contrary, the 800 mg dose always induced an immediate, effective and prolonged antacid action, reaching a maximum pH value of 5 and lasting up to 40 minutes. Our study confirms, using a modern and reliable technique as the 24-hour gastric pH-metry, the antacid activity of magnesium hydroxide.

Adult

The effect of a sodium citrate preparation compared with an aluminium-magnesium hydroxide preparation on the urinary pH of normal subjects.

The effects of a sodium citrate preparation in two dosage regimens (4 g 4 times daily and 8 g 4 times daily) and of an aluminium-magnesium hydroxide suspension (15 ml 4 times daily) on the urinary pH of 19 healthy subjects were compared. The sodium citrate preparation in both dosages proved to be superior to the aluminium-magnesium hydroxide suspension in elevating the urinary pH. Urinary pH values as high as 8 were reached with the sodium citrate preparation. Blood pH, blood gases and electrolyte changes were within normal limits.

Adult

[Magnesium hydroxide and aluminum hydroxide in the treatment of gastroesophageal reflux].

Fifteen children with gastro-esophageal reflux took part in a treatment trial with a regimen of magnesium hydroxide and aluminium hydroxide for 8 weeks period (700 mmol/1.73 mq/die). All children were evaluated clinically and underwent a 24-hour continuous esophageal pH-monitoring both at diagnosis and after 8 weeks of treatment. After therapy 12/15 children were cured and 3/15 improved. Moreover the total percentage of time during which pH was less than 4, the number of reflux episodes and the number of refluxes lasting than 5' recorded during 24-hour continuous esophageal pH-monitoring were significantly reduced after treatment. The Authors conclude that antacids in large quantities are effective in medical treatment of gastro-esophageal reflux.

Aluminum Hydroxide

Magnesium intoxication in a neonate from oral magnesium hydroxide laxative.

This is a case of magnesium intoxication in a neonate produced by an oral magnesium cathartic. A review of the literature revealed there are very few cases that have been reported of magnesium toxicity due to cathartics. There is no recommended dose for magnesium cathartics in neonates or data on their safety. A review of the management of magnesium intoxication is presented.

Administration, Oral

Influence of dielectric constant on sedimentation rate of concentrated suspensions of aluminum and magnesium hydroxides.

Sedimentation of dilute pharmaceutical suspensions obeys Stokes's law, which assumes that there is no interaction between particles. The behavior of concentrated pharmaceutical suspensions is generally interpreted by use of modifications of Stokes's law that do not consider chemical interaction between particles. Properties of the medium itself, such as dielectric constant and surface tension, have not been included in the established equations. The present work shows that the dielectric constant of the medium has a distinct effect on the rate of sedimentation of the systems investigated.

Aluminum Hydroxide

Magnesium hydroxide: new insights into the mechanism of its laxative effect and the potential involvement of prostaglandin E2.

The mechanism by which Mg(OH)2 acts as a laxative is unknown. To explore the mechanism, six volunteers more than 55 years old, with normal bowel habits, were enrolled in a dose-response, randomized, placebo-controlled, double-blind, crossover design study. Each subject was studied for four inpatient periods of 5 days each on a metabolic ward with 9 days off of all medication between studies. In the hospital, all patients were on a diet fixed in calories, fluid volume, Na+, fiber, and Ca2+. At 8 p.m. on each study day, each subject took 45 ml containing either placebo or 1,200, 2,400, or 3,600 mg of Mg(OH)2 plus 240 ml of water. On the fourth and fifth hospital days of each period, 24-h stool output was quantified and analyses performed. Compared to placebo, Mg(OH)2 caused the following dose-dependent results: (a) increased number of bowel movements; (b) increased percentage of stool water; (c) increased stool volume; (d) increased stool Mg2+; and (e) increased total stool 24-h prostaglandin E2 (PGE2), with mean 24-h excretions as follow: placebo, 95 +/- 18 pg/24 h; 1,200 mg Mg(OH)2, 260 +/- 100; 2,400 mg Mg(OH)2, 357 +/- 117; and 3,600 mg Mg(OH)2, 525 +/- 196. There was a significant correlation between stool PGE2 excretion and stool water consistent with a causative relationship. However, the concentration of stool prostaglandin was lower than the concentration found to alter intestinal electrolyte transport in vitro. In summary, the laxative effect of Mg(OH)2 is associated with increased output of stool PGE2. The contribution of the stool PGE2 to the laxative effect of Mg(OH)2 is unknown.

Cathartics

The effect of an antacid on the bioavailability of indomethacin.

The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significantly only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.

Adult

Nizatidine versus placebo in active benign gastric ulcer disease: an eight-week, multicenter, randomized, double-blind comparison. The Nizatidine Benign Gastric Ulcer Disease Study Group.

STUDY OBJECTIVE: To determine if 150 mg nizatidine twice daily or 300 mg nizatidine at bedtime are similarly effective and to compare each dose with placebo in healing benign gastric ulcers and relieving peptic ulcer symptoms. METHODS: This study was a randomized, double-blind, placebo-controlled parallel comparison. The study was conducted at 74 gastroenterology and internal medicine clinics in the United States and Canada. Four hundred fifty-six patients with active benign gastric ulcer documented by endoscopy participated in the study. On the basis of a computer-generated randomization list, patients were assigned sequentially to receive either 150 mg nizatidine twice daily (n = 151), 300 mg nizatidine once daily at bedtime and identically appearing placebo capsules in the morning (n = 153), or placebo capsules twice daily (n = 152). Treatment lasted for 8 weeks unless healing was documented by endoscopy after 4 weeks. Antacid tablets (aluminum hydroxide, magnesium hydroxide, simethicone combination) were supplied for relief of symptoms. MEASUREMENTS AND MAIN RESULTS: Both doses of nizatidine significantly improved healing rates at 8 weeks compared with placebo. Daytime and nighttime symptom severity was improved by both nizatidine regimens at end point (p less than 0.015 versus placebo, two-tailed test). Antacid use was similar for all groups in the end point analysis. Patient well-being was significantly better in patients treated with nizatidine than in patients in the placebo group ((p less than 0.04, two-tailed test). No clinically significant differences in the incidence of adverse clinical or laboratory events were noted. CONCLUSION: Nizatidine, 300 mg at bedtime and 150 mg twice daily, resulted in greater healing of benign gastric ulcers than placebo treatment after 8 weeks. Relief of the symptoms of gastric ulcer was significantly better in the patients receiving nizatidine treatment versus placebo treatment.

Capsules

Stability of nizatidine in extemporaneous oral liquid preparations.

The stability of nizatidine in extemporaneous oral liquid preparations stored at room and refrigerated temperatures was studied. Preparations containing nizatidine in a final concentration of approximately 2.5 mg/mL were made by mixing the contents of a 300-mg nizatidine capsule with commercial juices (Gatorade, Stokely-Van Camp; Cran-Grape, Ocean Spray; apple juice, Sundor Brands; and V8 vegetable juice, Campbell Soup) and with aluminum hydroxide-magnesium hydroxide suspension (Maalox, Rorer). A control solution was prepared in water. Samples of each preparation were stored at 15-30 degrees C and at 5 degrees C. Initially and after 4, 8, 24, and 48 hours of storage, the samples were visually inspected, tested for pH, and analyzed in triplicate by high-performance liquid chromatography for nizatidine content. No appreciable changes in appearance or pH occurred. The only extemporaneous preparations with greater than 10% loss of nizatidine potency at 48 hours were the Cran-Grape and V8 preparations at room temperature. There was no correlation between pH of the preparations and changes in drug concentration. In the Maalox and V8 preparations, the drug powder did not dissolve uniformly. In all the preparations tested, nizatidine was stable for at least eight hours at refrigerated and room temperatures. In all except the Cran-Grape and V8 preparations, the drug was stable for 48 hours under both storage conditions.

Administration, Oral