Effect Of Antacids Research Articles

Effects of OTC famotidine and antacid on gastric acid

Effects of OTC famotidine and antacid on gastric acid

徐放性ニフェジピン細粒製剤（ＫＢ−１７１２Ｐ）の血しょう中濃度に及ぼす制酸剤の影響

徐放性ニフェジピン細粒製剤（ＫＢ−１７１２Ｐ）の血しょう中濃度に及ぼす制酸剤の影響

Effects of the Antacids in Didanosine Tablets on Dapsone Pharmacokinetics

To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV). Two separate, randomized, two-period, two-treatment, crossover studies with a 21-day washout period between treatments. Clinical investigation unit of a university hospital. Six healthy men and six HIV-positive men. Serial dapsone plasma concentrations were measured when dapsone, 100 mg, was administered alone and with either the third of four doses of didanosine placebo tablets (group 1) or the 27th of 28 doses of active didanosine tablets (group 2). In each study, pharmacokinetic variables were determined using noncompartmental methods and compared by analysis of variance. When dapsone was administered alone, pharmacokinetic variables did not significantly differ from those with dapsone given in either combination (P > 0.10 for all comparisons). Didanosine, antacids, and other excipients in the currently used didanosine chewable tablets did not significantly affect plasma concentrations of dapsone.

Augmentation of the antacid effect of omeprazole by Helicobacter pylori infection in duodenal ulcer disease: [formula omitted], A.L. Blum, J.P. Idström, E. Verdu, M. Stolte, B. Tillenburg, M. Sollböhmer, G. Börsch. Dept. of Medicine, Elisabeth Hospital Essen, Germany

Augmentation of the antacid effect of omeprazole by Helicobacter pylori infection in duodenal ulcer disease: [formula omitted], A.L. Blum, J.P. Idström, E. Verdu, M. Stolte, B. Tillenburg, M. Sollböhmer, G. Börsch. Dept. of Medicine, Elisabeth Hospital Essen, Germany

マクロライド系抗生物質の体内動態に及ぼす制酸剤併用の影響

マクロライド系抗生物質の体内動態に及ぼす制酸剤併用の影響

Enhancement of drug absorption by antacids. An unrecognised drug interaction.

Antacids are widely used for many disorders. The potential of antacids to interact with other concomitantly ingested drugs is well recognised. These interactions usually result in reduced or delayed absorption of the affected drug. However, this is not always the case. In contrast to aluminium hydroxide, magnesium hydroxide and sodium bicarbonate can enhance the absorption of some drugs. For example, magnesium hydroxide can increase the rate and sometimes even the extent of absorption of certain nonsteroidal anti-inflammatory drugs (e.g. tolfenamic acid, mefenamic acid and ibuprofen), sulphonylurea antidiabetic agents [e.g. glipizide, glibenclamide (glyburide) and tolbutamide] and the oral anticoagulant dicoumarol (bishydroxycoumarin). These weakly acidic drugs are nonionised at gastric pH, but are sparingly water soluble. Elevation of the gastric pH by administration of magnesium hydroxide or sodium bicarbonate increases the solubility and absorption of such sparingly water soluble agents. Chelate formation may be involved in the increased absorption of dicoumarol by magnesium hydroxide. In combination antacids containing both aluminium hydroxide and magnesium hydroxide, the absorption enhancing effect of magnesium hydroxide seems to be counterbalanced by the opposing effects of aluminium hydroxide. The clinical significance of increased drug absorption is not clear. However, accelerated and enhanced absorption of analgesic drugs may be beneficial when rapid pain relief is desired. In contrast, an unexpectedly increased hypoglycaemic or anticoagulant effect may be potentially dangerous. Therefore, a knowledge of the potential effect of antacids on the absorption of other drugs is clinically important.

Ondansetron Absorption in Adults: Effect of Dosage Form, Food, and Antacids

Ondansetron is a competitive serotonin 5‐HT3receptor blocker that has proved useful in the prevention of emesis due to cisplatin and other cancer chemotherapeutic agents. In a randomized, open‐label, crossover study in 24 healthy male subjects, the relative bioavailability of a single 8‐mg tablet was compared with that of an 8‐mg solution using the two one‐sidedt‐tests. The tablet and solution formulations were bioequivalent, as confirmed by similarities in meanCmax(26.3 vs 27.7 ng/mL),Tmax(1.79 vs 1.70 h), and AUC (166.0 vs 167.3 ng‐h/mL) values. In another randomized, open‐label, crossover study in 12 healthy male subjects, the bioavailability of an 8‐mg ondansetron tablet administered 5 min after a standard meal was slightly but significantly greater than in fasted subjects, as indicated by comparative mean AUC values [201.4 ng‐h/mL (fed) vs 172.5 ng‐h/mL (fasted)]. Coadministration of a magnesium hydroxide/aluminum hydroxide antacid did not affect the bioavailability of the ondansetron tablet.

Pharmacokinetics of Gyrase Inhibitors, Part 1: Basic Chemistry and Gastrointestinal Disposition

This review describes the physicochemistry and pharmacokinetic principles of gyrase inhibitors in relation to their distribution in the gastrointestinal tract. Their basicity and lipophilicity at physiologic pH, which affect their disposition in the gastrointestinal tract, are weakened or strengthened by substitutions on the quinoline nucleus. Heterocyclic substitution at position 7 significantly increases basicity and affects lipophilicity considerably. At physiologic pH, the 3-carboxyl group adds significant negative charge. The balance between the negatively charged carboxyl group and the positively charged heterocycle substitutions determines the pH-dependent ratio between ionized and un-ionized species and the solubility and lipophilicity of gyrase inhibitors. After oral administration, both the maximal plasma concentration (Cmax) and time to reach this value (Tmax) are affected primarily by the absorption constant. Absorption of N4'-methylated gyrase inhibitors tend to be greater than that of nonmethylated compounds. Acid-base properties affect absorption as do solubility and dissolution rates. Gyrase inhibitors probably are absorbed primarily in the upper gastrointestinal tract. Food does not alter overall absorption of several gyrase inhibitors studied but prolongs the Tmax slightly but significantly. N4'-methylation appears to protect against effects of food. Delay in gastric emptying may cause the increase in Tmax of gyrase inhibitors ingested with fatty meals. Effects of antacids on absorption of gyrase inhibitors depend on the interval between administration. Other ions also may reduce the absorption of gyrase inhibitors, but histamine-2 (H2)-antagonists appear to affect intestinal absorption of some, but not all, gyrase inhibitors. Gyrase inhibitors undergo significant gastrointestinal elimination.

Role of eicosanoids, nitric oxide, and afferent neurons in antacid induced protection in the rat stomach.

The mechanism underlying the mucosal protective effect of antacids is still unclear. This study shows that in rats the aluminum containing antacid, hydrotalcit, induces dose dependent protection against gastric mucosal damage caused by ethanol or indomethacin which is considerably enhanced by acidification. Hydrotalcit did not increase gastric mucosal formation or the intraluminal release of prostaglandins, and did not prevent the increase in mucosal leukotriene C4 formation in response to ethanol. Pretreatment with indomethacin did not attenuate the protective effect of unmodified or acidified hydrotalcit. Furthermore, hydrotalcit significantly reduced the gastric damage caused by indomethacin even when it was administered up to 2 hours after the ulcerogen. In indomethacin treated rats, simultaneous administration of hydrotalcit did not affect the concentrations of indomethacin in serum or inflammatory exudates nor did it attenuate the inhibition of prostaglandin release into the exudates. In hydrotalcit treated rats there was no attenuation of the increase in sulphidopeptide leukotriene release or decrease in leukocyte influx into inflammatory exudates elicited by indomethacin administration. Functional ablation of afferent neurons and inhibition of endogenous nitric oxide partially antagonised the protective effect of unmodified, but not of acidified, hydrotalcit. It is concluded that (i) the protective effect of unmodified and acidified hydrotalcit is independent of the eicosanoid system; (ii) protection against indomethacin induced gastric lesions does not require treatment before dosing of the ulcerogen and does not interfere with absorption and anti-inflammatory actions of indomethacin; (iii) endogenous nitric oxide and afferent neurons contribute partly to the effect of unmodified, but not of acidified, hydrotalcit suggesting that different mechanisms mediate their mucosal protective activity.

Effects of aluminium-containing antacid on bioavailability of ofloxacin following oral administration of pivaloyloxymethyl ester of ofloxacin as prodrug.

We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al3+, Mg2+, Ca2+, or Fe2+ in the gastrointestinal tract. This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes. In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion. Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX. Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits. The area under the plasma concentration-versus-time curve from zero to 24 h (AUC0-24h) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC0-24h values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone. These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations.

The effect of antacid on aspirin pharmacokinetics in healthy Thai volunteers.

The effect of antacid on aspirin pharmacokinetics and bioavailability was determined in 10 healthy adult male and female volunteers, aged 20-45 years old. Each subject received 650 mg of aspirin orally after an overnight fast. The wash out period was 14 days and then all subjects were given 650 mg of aspirin 10 minutes after antacid (aluminium hydroxide and magnesium hydroxide). Plasma aspirin, salicylate and salicyluric acid levels were determined by a specific high performance liquid chromatographic analysis. Individual plasma profiles were analysed using compartmental and non-compartmental methods. The results show that antacid affected the relative bioavailability of aspirin since the mean peak concentration (Cmax) of aspirin was significantly higher when antacid was given. However, the time to reach peak concentration (Tmax) and the area under the plasma concentration-time curve (AUC) showed no significant difference between the two treatments. It was, therefore, not possible to conclude that the non-bioequivalence was caused by a difference in rate or amount of aspirin absorption, or both. No significant difference was observed in Cmax, Tmax, AUC, t1/2, Ka, Kel of salicylate and salicyluric acid. However, the rate of total salicylate absorption was increased since the absorption rate constant (Ka) was higher when antacid was given. This may provide a more rapid effect of the drug.

An artificial stomach-duodenum model for the in-vitro evaluation of antacids.

To improve the dynamic in-vitro evaluation of the effects of antacids, we have developed the 'artificial stomach' model by adding a 'duodenal reservoir' to receive the gastric emptying flux and simulated bicarbonate secretion, thus constituting an 'artificial stomach-duodenum' model. With this model we measured antacid-induced resistance to gastric acidification, and simultaneously evaluated the effect of antacid activity on the duodenal milieu. The model also permitted evaluation of the antacid effects of proteins (as natural antacids), and of drugs containing aluminium phosphate, alone or combined with magnesium oxide, or aluminium and magnesium hydroxides. At the gastric site, these drugs, as well as the proteins (that is, meat extract), induced a strong resistance to acidification due to the gastric emptying flux and to antacid composition. At the duodenal site, the decrease of the acid load penetrating into the duodenum varied, depending on the efficacy of gastric antacid activity. Duodenal pH was related to the equilibrium between bicarbonate secretion and the emptying of acid load. Proteins and aluminium phosphate induced the same duodenal pH as in the control tests without antacids, but magnesium-containing antacids increased it, thus decreasing bicarbonate consumption. The antacid mechanisms within the stomach, and the fate of antacids in the duodenal milieu, might explain the variation in duodenal pH in response to antacid administration.

Effect of antacid on absorption of the quinolone lomefloxacin.

The effect of antacid on the absorption of lomefloxacin (LFLX) in humans was studied. When LFLX was orally administered concomitantly with aluminum- and magnesium-containing antacids under fasting conditions, its level in plasma decreased by one-half and its area under the concentration-time curve was reduced by 40% compared with the levels observed after treatment with LFLX alone. The urinary recovery value also decreased by 40%. No such effects were noted after coadministration of LFLX and a nonmetallic antacid. This study confirmed the existence of chelate complexes of LFLX with Al3+ and Mg2+ and examined the chelating strength. The stability constants of LFLX with Al3+ and Mg2+ were measured and compared with those of ofloxacin and norfloxacin; little difference was observed among them. LFLX was found to bind more strongly with Al3+ than with Mg2+. Further, the existence of chelate formation was proven by 13C-nuclear magnetic resonance spectroscopy. The decrease in the LFLX level in plasma in humans could be explained by a reduced absorption of the Al(3+)- and Mg(2+)-LFLX chelate complexes.

Effect of antacid on the bioavailability of cefprozil.

The effect of antacid on the bioavailability of cefprozil was investigated in a two-way crossover study. Eight healthy male subjects received a single 500-mg oral dose of cefprozil with and without coadministration of 30 ml of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (Maalox). Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. When cefprozil was administered alone (treatment A), the mean maximum concentrations (Cmax) of the cis and trans isomers were 9.2 and 1.2 micrograms/ml, respectively. When cefprozil was coadministered with Maalox (treatment B), the Cmax values of the cis and trans isomers were 8.7 and 1.3 micrograms/ml, respectively. The mean values of the area under the curve from time zero to infinity (AUC0-infinity) were 27.7 and 3.5 micrograms.h/ml for treatment A and 27.5 and 3.5 micrograms.h/ml for treatment B for the cis and trans isomers, respectively. The other pharmacokinetic parameters, time to Cmax, elimination half-life, mean residence time, renal clearance, and percent urinary excretion, were essentially the same for the two isomers. The respective values of the elimination half-life for the cis and trans isomers were 1.36 and 1.32 h for treatment A and 1.36 and 1.42 h for treatment B. Mean urinary excretion was 63 and 60% for treatment A and 58 and 56% for treatment B for the cis and trans isomers, respectively. No significant differences between the two treatments were found for any of the pharmacokinetic parameters for either isomer. For the cis isomer, bioavailability point estimates (90% confidence intervals) of the mean Cmax and AUG0-infinity values for the Maalox treatment relative to those for the reference treatment were 95% (87%, 103%) and 99% (95%, 104%), respectively. For the trans isomer, the value were 109% (92%, 126%) for Cmax and 97% (88%, 106%) for AUC0-infinity. On the basis of the results of this study, it is concluded that the bioavailability of cefprozil is not affected by the coadministration of Maalox.

Effects of antacid and probenecid on gastrointestinal absorption and renal excretion of Y-26611 in healthy humans

Effects of antacid and probenecid on gastrointestinal absorption and renal excretion of Y-26611 in healthy humans

Kinetics and effectiveness of aluminium hydroxide gels: 1.-Synthesized at different values of pH.

AbstractThe antacid effectiveness and kinetic behaviour of three aluminium hydroxide gels, synthesized at different values of pH of precipitation, have been studied with the pH-Stat technique. Results indicate that these properties improve with increasing pH of precipitation and are structure related.

The hypocholesterolemic effect of an antacid containing aluminum hydroxide

study objective: To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. design: A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. setting: Family practice clinics of two rural communities (kibbutzim) in Israel. patients: Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. intervention: After 2 months of dietary modification (low-fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. measurements and main results: Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p <0.001) and 18.5% after 4 months (p <0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked placebo phase. Although the high-density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p <0.05). The treatment was well tolerated, with minimal side effects. conclusions: An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients.

Nosocomial Pneumonia and the Role of Gastric pH: A Meta-Analysis

Purpose To examine the differential effect of drugs used for stress ulcer prophylaxis on nosocomial pneumonia in critically ill patients. Data Identification Computerized bibliographic search of published and unpublished research. Study Selection Independent review of 48 randomized controlled trials of prophylaxis identified eight relevant studies. Data abstraction The population, intervention, and outcomes were evaluated by duplicate independent review. Results The incidence of pneumonia was lower in critically ill patients receiving antacids and/or histamine-2-receptor antagonists as compared with patients receiving no stress ulcer prophylaxis (common odds ratio 0.42, 95 percent CI 0.17 to 1.11). When stress ulcer prophylactic therapy was titrated to achieve a gastric pH of 3.5 or greater, there was a trend favoring a decreased incidence of pneumonia (0.66, 95 percent CI 0.24 to 1.78). In trials comparing sucralfate with pH-altering drugs, the common odds ratio of 0.55 (0.28 to 1.06) suggests a 45 percent risk reduction with the use of sucralfate. Conclusion Stress ulcer prophylaxis with drugs which raise gastric pH does not increase the incidence of pneumonia in comparison to placebo or control therapy. The use of sucralfate is associated with a lower incidence of nosocomial pneumonia in comparison to agents which raise gastric pH. However, methodologic deficiencies, small sample sizes, and the failure to examine the effects of antacids and histamine-2-receptor antagonists separately make a large prospective randomized trial necessary to confirm or refute these findings. To examine the differential effect of drugs used for stress ulcer prophylaxis on nosocomial pneumonia in critically ill patients. Computerized bibliographic search of published and unpublished research. Independent review of 48 randomized controlled trials of prophylaxis identified eight relevant studies. The population, intervention, and outcomes were evaluated by duplicate independent review. The incidence of pneumonia was lower in critically ill patients receiving antacids and/or histamine-2-receptor antagonists as compared with patients receiving no stress ulcer prophylaxis (common odds ratio 0.42, 95 percent CI 0.17 to 1.11). When stress ulcer prophylactic therapy was titrated to achieve a gastric pH of 3.5 or greater, there was a trend favoring a decreased incidence of pneumonia (0.66, 95 percent CI 0.24 to 1.78). In trials comparing sucralfate with pH-altering drugs, the common odds ratio of 0.55 (0.28 to 1.06) suggests a 45 percent risk reduction with the use of sucralfate. Stress ulcer prophylaxis with drugs which raise gastric pH does not increase the incidence of pneumonia in comparison to placebo or control therapy. The use of sucralfate is associated with a lower incidence of nosocomial pneumonia in comparison to agents which raise gastric pH. However, methodologic deficiencies, small sample sizes, and the failure to examine the effects of antacids and histamine-2-receptor antagonists separately make a large prospective randomized trial necessary to confirm or refute these findings.

Drug Interaction With Quinolone Antibiotics in Intensive Care Unit Patients

<h3>To the Editor. —</h3> It is not uncommon for the patients in an intensive care unit to become colonized with resistant organisms after a course of antibiotics. These organisms are frequently resistant to most antibiotics, and ciprofloxacin often becomes one of the few options for oral treatment. The majority of the patients in the intensive care unit, however, also receive prophylactic antacid therapy to prevent stress ulcers. Despite the profound negative effect of antacids or sucralfate on the absorption of ciprofloxacin,^1,2an effort to avoid this significant drug-drug interaction to ensure adequate drug levels does not always seem to occur when the antibiotic or antacid treatment is initiated. We reviewed retrospectively the medication orders for our intensive care unit patients to determine the incidence of this combination. During a 3-month period (November 1989 to January 1990), ciprofloxacin was prescribed in 54 intensive care unit patients. In 41 of these

Effect of Misoprostol and Antacids on Gastric and Duodenal Mucosal Enzyme Activities in Duodenal Ulcer Patients

The activities of 11 marker enzymes from the gastric and duodenal mucosa were determined in 15 patients with active duodenal ulcer disease before therapy, after 4 weeks of therapy with the prostaglandin E1 analogue misoprostol, 400 micrograms twice daily, and after another 4 weeks without any therapy. Another 15 patients were given a high-dose liquid antacid regimen. The activities were measured in homogenized material obtained with forceps through an endoscope. The healing rates of the two groups at 4 weeks were 53% and 80%, respectively. No changes in mucosal inflammation were noted during therapy. During treatment with misoprostol the activities in the descending duodenum of the membrane enzymes alkaline phosphatase, leucyl-beta-naphthylamidase, gamma-glutamyltransferase, and 5'-nucleotidase increased towards the values seen in normal controls. Despite a higher healing rate, no changes in the enzyme activities occurred in the group given high-dose antacid therapy. Four weeks after cessation of therapy the enzyme activities in the misoprostol group were not significantly different from the pretreatment values. In the biopsy specimens from the duodenal bulb the activities of monoamine oxidase fell during treatment with misoprostol and were restored to the pretreatment activity when therapy was stopped. In the stomach mucosa the enzyme activities were largely unchanged during treatment with both misoprostol and antacids. These results indicate that misoprostol and antacids have different mechanisms of action but may also suggest that the demonstrated enzymic changes are unrelated to the healing process.