Dose Of Antacid Research Articles

Association of acid-suppressive therapy and tuberculosis: A causal or coincidental link to the infection?

BackgroundAcid-suppressant proton-pump inhibitors (PPI) and histamine-2-receptor antagonists (H2RA) are associated with an increased risk of tuberculosis (TB). However, it remains unclear whether this association is causal or coincidental. MethodsPatients newly diagnosed with TB between 2000 and 2013 were identified from the Taiwan National Health Insurance Database. Each patient with TB was matched in a 1:10 ratio with patients without TB by age, sex, and index date. The time lags from the end of PPI or H2RA treatment to the index date, and respective cumulative doses in the 90 days before the index date, were analyzed for association with TB. ResultsThe age (mean [standard deviation] 60.8 [17.3] years) and sex ratio (69.4% males) were comparable between patients with TB (n = 6002) and patients without TB (n = 60,020). Previous PPI or H2RA treatment was more frequently observed in patients with TB (16.6% vs. 8.9%, p < 0.001). Concurrent antacid therapy posed the highest risk for TB (odds ratio [OR] 4.21 for PPI and 2.24 for H2RA, both p < 0.0001), and the closer to the end of the therapy, the more likely TB was detected (p for trend: 0.0077 for PPI and 0.0145 for H2RA). The cumulative doses of antacid in the 90 days before TB had an inverse relationship with TB risk. PPI, used either alone or in combination with H2RA, conferred a higher risk of TB than H2RA alone. ConclusionsTuberculosis should be considered in symptomatic patients receiving or recently ceased antacid therapy with PPI or H2RA in TB endemic areas.

The comparison of gastric ph after premedication using ranitidine, antacids, and ranitidine-antacids combination in cesarean section

Background: Pregnant women are at high risk of experiencing gastric fluid aspiration, which is known as Mendelson's syndrome. The possibility of aspiration increases in an emergency condition. Low pH and high volume of aspirate increase the severity of aspiration. Ranitidine and antacids can increase gastric pH. This study aimed to compare gastric pH after receiving ranitidine, antacids, and ranitidine-antacids combination as premedication in patients undergoing an emergency cesarean section (C-section). Patients and Methods: This study is a true-experimental design on 27 participants who underwent a C-section at Dr. Saiful Anwar Hospital. The R group received ranitidine 50 mg, the A group received 10 ml of antacids, and the C group received the combination of both. The measurement of gastric pH was carried out on 0, 5, 15, 30, 45, and 60 min after premedication. The data were analyzed using the one-way ANOVA test. Results: The average change in gastric pH is better seen in the antacids group. The gastric pH increases from 3.19 ± 1.04 to 4.64 ± 1.20 at 60 min after premedication (P > 0.05). Ranitidine administration showed better results at 5, 15, and 30 min after premedication (P > 0.05). The combination of ranitidine and antacids showed better results at 45 and 60 min after premedication (P > 0.05). Conclusion: There is no significant difference in gastric pH after receiving premedication in patients undergoing a C-section. However, all groups show an increase in gastric pH after receiving premedication. The administration of ranitidine and antacids combination is not better than a single dose of ranitidine or antacids.

Effects of Food and Antacids on Pharmacokinetics and Pharmacodynamics of Lesinurad, a Selective Urate Reabsorption Inhibitor.

Two clinical studies were performed in healthy volunteers to investigate food and antacid effects on lesinurad, a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. Study 1 evaluated a high-fat, high-calorie meal or high doses of antacids (3000mg calcium carbonate or 1600mg magnesium hydroxide/1600mg aluminum hydroxide) on the pharmacokinetics (PK) and pharmacodynamics (PD) of 400mg oral lesinurad. Study 2 evaluated low doses of antacids (1250mg calcium carbonate or 800mg magnesium hydroxide/800mg aluminum hydroxide) on the PK and PD of 400mg lesinurad. Food did not alter the plasma AUC of lesinurad and only reduced its Cmax by 18%. In the fasted conditions, high-dose calcium carbonate reduced the Cmax and AUC of lesinurad by 54% and 38%, respectively, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced Cmax and AUC by 36% and 31%, respectively. Food enhanced the maximum serum urate (sUA)-lowering effect of lesinurad by approximately 20% despite reducing the Cmax of lesinurad. High-dose calcium carbonate decreased the urate-lowering effect approximately 20% in the first 6hours, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced the effect by 26%. Low-dose calcium carbonate or magnesium hydroxide/aluminum hydroxide in the presence of food did not significantly affect plasma lesinurad Cmax and AUC or the sUA lowering and renal handling of uric acid. In summary, study results suggest food did not meaningfully alter lesinurad PK and PD. High doses of antacids reduced lesinurad AUC up to 40% and reduced the lesinurad uric acid-lowering effect.

Hayatı Tehdit Eden Hiperkalsemi ile Başvuran Hipoparatiroidi Olgusu

Milk-alkali syndrome was first described in patients using high dose antacid drugs for peptic ulcer. The triad of the syndrome is hypercalcemia, metabolic alkalosis, and acute renal failure. The incidence of the syndrome that decreased after the development of modern ulcer treatments has currently been increasing again due to the use of calcium-containing medicine for osteoporosis and renal osteodystrophy. In this report, we present a patient who had been under calcium carbonate and active vitamin D treatment due to idiopathic hypoparathyroidism and presented with life-threatening hypercalcemia, metabolic alkalosis, and acute renal failure.

The Case Files

FigureFigureFigureFigureA previously healthy 17-year-old girl presented to the ED with one month of intermittent, burning epigastric pain associated with nausea and vomiting. Pain was worsened by spicy, greasy foods, and alleviated by sparkling water. She said she came to the ED because the pain had persisted for a while and was interfering with her life. The patient denied fevers, recent travel, or a change in bowel movements. She admitted to traveling to Nicaragua many times in her life and to an unintentional 20-pound weight gain over the past year. Vitals at presentation were a heart rate of 83 bpm, temperature of 36.6°C, blood pressure of 114/62 mm Hg, and respiratory rate of 20 bpm. Physical exam was significant only for a slightly enlarged nontender thyroid gland and mild epigastric and right upper quadrant tenderness to palpation. The RUQ tenderness on exam prompted a bedside ultrasound to explore for cholelithiasis, choledocolithiasis, cholecystitis, and hepatitis. It showed a gallbladder with a Phrygian cap that appeared normal and a white hyperechoic lesion in the liver that prompted an abdominal ultrasound by an ultrasound tech and a reading by a radiologist. The patient received one dose of antacids for her abdominal pain, which she said resolved her symptoms. The ultrasound revealed a normal gallbladder and a liver mass characterized as an ill-marginated 3.5 x 5.3 cm echogenic focus in the left lobe of the liver with peripheral hypoechogenicity with internal central vascularity shown by color Doppler. (Shown.) The radiologist recommended an MRI with liver mass protocol to evaluate the lesion. Labs sent by the ED were unremarkable, including a normal coagulation profile, CBC, and CMP. The patient was admitted for further workup of the unspecified liver mass, for which the differential diagnosis included hemangioma, adenoma (though the patient was not on oral contraceptives), hepatocellular carcinoma, hydatid cyst, and focal nodular hyperplasia. Fortunately for her, the MRI showed focal nodular hyperplasia (FNH). (Shown.) She was seen by the pediatric gastroenterology team, and was discharged with follow-up to monitor the FNH.FigureFigureFNH is the second most common liver tumor. (Cancer 1980;46[2]:372.) It is believed to occur as a response by hepatocytes to underlying congenital AV malformation. Women with FNH are at risk of developing hemorrhagic foci within the liver when on oral contraceptives. FNH is generally benign other than that increased risk. (Mod Pathol 1989;2[5]:456.) It is important to characterize a liver lesion as FNH to save a patient from unnecessary liver biopsy. The patient had a benign liver lesion, but this case still highlights the important role bedside ultrasound can play in the evaluation, workup, and management of common symptoms presenting to the ED.

Antacid attenuates the laxative action of magnesia in cancer patients receiving opioid analgesic.

ObjectiveThis study was designed to investigate pharmacological interaction between magnesium laxative and antacid in patients receiving opioid analgesic.MethodsData obtained from a total of 441 eligible patients receiving opioid analgesic for the first time were retrospectively analysed. The incidence of constipation, defined as stool‐free interval of 3 days and more within the first week of opioid intake, was compared between patients who took laxative alone and those who received laxative in combination with antacid.Key findingsLaxatives were prescribed in 74% of patients, among them 61% received antacids such as proton pump inhibitor and H2 receptor blocker. Magnesia was the most commonly used laxative (89%). Constipation occurred in 21% and 55% of patients with and without laxatives, respectively. Antacids reversed the laxative action of lower doses (<2000 mg/day) but not higher doses (>2000 mg/day) of magnesia without affecting the effects of other laxatives. Therefore, it is suggested that both acid‐dependent and acid‐independent mechanisms may operate in the laxative action of magnesia, in which the former may be involved in the action of lower doses of magnesia.ConclusionCare should be taken to avoid the unfavourable pharmacological interaction between low doses of magnesia and antacid.

World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease.

PROBIOTICS—THE CONCEPTHistory and DefinitionsA century ago, Elie Metchnikoff (a Russian scientist, Nobel laureate, and professor at the Pasteur Institute in Paris) postulated that lactic acid bacteria (LAB) offered health benefits capable of promoting longevity. He suggested that “intestinal autoint

Multiple dose of liquid antacid enhance simvastatin bioavailability in Malaysian male volunteers

Multiple dose of liquid antacid enhance simvastatin bioavailability in Malaysian male volunteers

1484PD - Selective Internal Radiation Therapy (SIRT) for Gist Liver Metastases Resistant to Tyrosine Kinase Inhibitors

ABSTRACT Background and aim The liver is the typical location of metastases from gastrointestinal stromal tumors (GIST). Usually, metastases of GIST are treated by tyrosine kinase inhibitors (imatinib, sunitinib or others). In patients with multiple metastases resistant to drugs and not amenable to surgical resection interventional ablation techniques are considered. Selective internal radiation therapy (SIRT), delivering 90Y-loaded particles to liver metastases might offer a new treatment option. Material/methods We evaluated nine patients with liver metastases of GIST being progressive under drug (TKI) treatment and referred for SIRT. Five patients had liver metastases only, in another four patients extrahepatic disease was present but controlled by TKI therapy. One patient had to be excluded from treatment due to a hepato-pulmonary shunt volume exceeding 20 %. Depending on intrahepatic tumor distribution, either both liver lobes or one lobe were treated using 90Y spheres. Follow-up was done via dynamic MRI, contrast-enhanced (CE)-CT and 18F-FDG-PET-CT using modified RECIST criteria at 3 months intervals. All patients with targetable mutations in KIT or PD continued with drug to control extrahepatic tumor spread. Results In the eight patients, fourteen liver lobes were treated with a mean activity of 1.07GBq per lobe. No severe side effects occured in 7/8 patients, while one male developed an ulcer of the stomach not responding to high dose antacid therapy. Radiation induced liver disease (RILD) was not observed. Three patients showed a complete remission (CR) whereas four other patients developed a partial remission (PR) and two patients had to be classified as stable disease (SD). Median follow-up interval is 16 months (range, 4 - 52 months). The mean progression free interval regarding hepatic disease was 9,6 months. Conclusion SIRT offers a safe and effective treatment option in patients with liver metastases from GIST being progressive under TKI treatment. Disclosure All authors have declared no conflicts of interest.

Safety of adjuvants and excipients in vaccines

Vaccines are named either for the antigen that they contain or the disease that they prevent, but they contain a number of excipients that serve to maintain proper pH, prevent microbial growth, act as stabilizers, or enhance the immune response to the vaccine. The objective of this article is to provide information for pharmacists who address patient concerns related to the safety of vaccine adjuvants and excipients and to offer suggestions and resources to address these issues in the community. Vaccine adjuvants improve the potency of vaccines, allowing for decreased doses of antigens or fewer doses in a vaccine series. Aluminum salts are the only vaccine adjuvant currently licensed in the United States and are included in vaccines such as Haemophilus influenzae type b, diphtheria–tetanus–acellular pertussis (DTaP), pneumococcal conjugate, hepatitis A, and hepatitis B. Aluminum adjuvants enhance phagocytosis of the vaccine antigen and inflammation that recruits immune cells.1 Aluminum is the most common metal found in nature. Aluminum can be neurotoxic and has been linked to dementia in patients with renal failure who receive large amounts of aluminum-containing antacids used as phosphate binders.2 This has led to the question of whether the amount of aluminum given to infants and children with the current vaccination schedule could lead to developmental delay or decreases in learning and memory. Patients can be assured that the amount of aluminum received during several vaccinations is well below the minimum risk level for daily intake. The aluminum exposure from vaccines in the first 6 months of life is about 4 mg. During this same time, the infant can be exposed to 10 mg aluminum in breast milk, about 40 mg in infant formula, or about 120 mg in soy-based formula. The aluminum exposure from a dose of vaccine is about 1,000 times less than the amount of aluminum from a dose of antacid.2 Aluminum has been used in vaccines for more than 75 years with hundreds of millions of doses given. Parents should be told that the aluminum can cause pain or redness around the injection site and in rare cases a harmless lump under the skin, but no long-term effects have been associated with aluminum in vaccines.3,4 Other compounds may be added to vaccines that are not adjuvants. For example, thimerosal is a preservative containing ethyl mercury that is no longer used as a preservative in childhood vaccines. It was reviewed in a previous installment of Vaccine Update.5 Formaldehyde is used during the manufacture of some vaccines to inactivate the pathogens. Although formaldehyde can cause cancerous changes to cells in vitro at certain doses, it does not have that property in either animals or humans. It is most widely known for its use as an embalming agent and as a component of cigarette smoke, which may alarm some patients. After manufacture and dilution, some vaccines (e.g. DTaP, hepatitis A, hepatitis B, polio) contain 0.1 mg formaldehyde or less per dose. This amount is 600 times less than has been given safely to animals and will not increase the patient’s risk for cancer or other ill effects.6 Some components of vaccines can elicit allergic responses ranging from mild to severe reactions, including anaphylaxis. Patients should be properly screened for all medication, food, and substance allergies using both openended questions and those that are vaccine specific. Latex can be found in some syringe plungers and in the rubber stoppers of some vaccine vials. For patients with a documented latex allergy, remove the rubber stopper of the vaccine or consider an alternate delivery technique to avoid adverse reactions. Latex content is described in prescribing information. Yellow fever and all influenza vaccine preparations are manufactured by using cellular components from chicken eggs that act as a viral growth medium during production. The final vaccine products contain measurable quantities of egg protein and should not be administered to any patient with a history of anaphylactic reaction to eggs. Influenza vaccine can be administered to individuals who can eat eggs.7 Gelatin is used in vaccines as a stabilizing agent and can be found in many commonly administered vaccines, including influenza (Fluzone brand), measles–mumps–rubella, varicella (Varivax), zoster (Zostavax), and DTaP (Tripedia brand). Gelatin has been estimated to cause immediate hypersensitivity reactions in approximately one person in every 2 million doses administered and is typically the responsible component when such reactions occur. Although immunizers can ask patients about allergies to food, the predictive value of this correlation is not very high.8 Another feature of vaccines that raises questions with patients is the presence of antibiotics. Many vaccines contain trace amounts of antibacterials such as neomycin, polymixin B, and streptomycin. These are used to prevent

Effect of an Aluminum‐ and Magnesium‐Containing Antacid on the Bioavailability of Garenoxacin in Healthy Volunteers

To evaluate the effect of an aluminum- and magnesium-containing antacid (Al-Mg antacid), which contains a high concentration of cations, on the pharmacokinetics of garenoxacin. Prospective, randomized, open-label, control-balanced, residual-effects-design study. Pharmaceutical company-affiliated study clinic. Twenty healthy volunteers who were garenoxacin naïve. Subjects were randomly assigned to receive three of six oral treatments, each separated by a 7-day washout period: garenoxacin 600 mg administered alone, with concomitant Al-Mg antacid, 2 or 4 hours before Al-Mg antacid, or 2 or 4 hours after Al-Mg antacid. The Al-Mg antacid dose was 20 ml, which contained aluminum hydroxide 900 mg and magnesium hydroxide 800 mg. The pharmacokinetics and safety of garenoxacin were assessed. For each treatment, serial blood samples for pharmacokinetic analysis of garenoxacin were collected before and up to 72 hours after garenoxacin dosing. Absence of effect of Al-Mg antacid on garenoxacin area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) and maximum observed plasma concentration (C(max)) were concluded if the 90% confidence interval of the adjusted geometric mean ratios with and without the antacid were contained within 0.80-1.25 and 0.70-1.43, respectively. Exposure to garenoxacin measured by AUC(0-infinity), a parameter well correlated with efficacy, was reduced by 58% when coadministered with Al-Mg antacid and reduced by 22% and 16% when administered 2 and 4 hours after the antacid, respectively. Administration of garenoxacin 4 hours before Al-Mg antacid had no effect on AUC(0-infinity) or C(max) of garenoxacin, whereas administration 2 hours before the antacid resulted in a nonclinically relevant (12%) reduction in AUC(0-infinity) of garenoxacin. Exposure to garenoxacin was significantly decreased when garenoxacin was coadministered with Al-Mg antacid or within 2 hours after the antacid. The magnitude of the changes in garenoxacin exposure suggests that garenoxacin should be administered at least 2 hours before or 4 hours after administration of Al-Mg antacid or other cation-containing products.

Clinical Pharmacokinetics and Gastrointestinal Tolerability of a Novel Extended-Release Microsphere Formulation of Azithromycin

A novel oral, extended-release, microsphere formulation of azithromycin (AZSR) was developed to improve the gastrointestinal tolerability profile while allowing administration of an entire treatment course of azithromycin in a single dose. Several phase I clinical pharmacology studies were conducted to (i) identify a well-tolerated single-dose formulation that met a predefined exposure target; and (ii) evaluate the effect of food and antacid on the absorption of this formulation. Of these, five pivotal studies are described here. The pharmacokinetic profile of AZSR was compared with that of the commercially available immediate-release azithromycin formulation (AZM) in an open-label, crossover, single-dose study (Study A), and their gastrointestinal tolerability profiles were compared in an observer-blind, parallel group, single-dose study (Study B). The effects of food (a high-fat meal and a standard meal) and antacid (a single 20 mL dose of Maalox Regular Strength, containing magnesium hydroxide, aluminium hydroxide and simethicone) on the absorption of azithromycin from AZSR were evaluated in three separate open-label, crossover, single-dose studies (Studies C, D and E). Healthy adult subjects were enrolled in all five studies, and all subjects were evaluable for tolerability. The dose used for all azithromycin formulations was 2.0 g. Serum azithromycin concentrations were determined using a validated high-performance liquid chromatography/electrochemical detection method, and pharmacokinetic parameters were analysed using noncompartmental methods. 377 subjects received a single 2.0 g dose of azithromycin as AZSR and/or AZM in the five studies. Compared with AZM, AZSR had a slower absorption rate (57% decrease in the mean peak concentration [C(max)] and an approximate 2.5-hour delay in the time to reach C(max) [t(max)]), with a mean relative bioavailability of 82.8%, which met the predefined exposure target (at least 80% bioavailability relative to AZM). Compared with AZM, AZSR was associated with significantly lower rates of nausea and vomiting. A high-fat meal increased the mean area under the serum concentration-time curve [AUC] from time zero to 72 hours post-dose (AUC(72 h)) by 23% and increased the C(max) of azithromycin by 115%. A standard meal increased the mean C(max) by 119% but had no clinically significant effect on the AUC(72 h). AZSR appeared to be better tolerated in the fasted state than in the fed state. The AUC(72 h) and C(max) of AZSR were not significantly affected by co-administration with a single dose of antacid. The extended-release microsphere formulation of azithromycin, AZSR, allows administration of an entire therapeutic course of azithromycin as a well-tolerated single 2.0 g dose. This formulation should be administered on an empty stomach and can be co-administered with antacids.

Inactivation of Escherichia coli O157:H7 in simulated human gastric fluid.

Human disease caused by Escherichia coli O157:H7 is a function of the number of cells that are present at potential sites of infection and host susceptibility. Such infectious doses are a result, in part, of the quantity of cells that are ingested and that survive human host defenses, such as the low-pH environment of the stomach. To more fully understand the kinetics of E. coli O157:H7 survival in gastric fluid, individual E. coli O157:H7 strains were suspended in various media (i.e., saline, cooked ground beef [CGB], and CGB containing a commercial antacid product [CGB+A]), mixed at various proportions with simulated human gastric fluid (SGF), and then incubated at 37 degrees C for up to 4 h. The highest inactivation rate among nine E. coli O157:H7 strains was observed in saline. Specifically, the average survival rates in 100:1 and 10:1 proportions of SGF-saline were -1.344 +/- 0.564 and -0.997 +/- 0.388 log(10) CFU/h, respectively. In contrast, the average inactivation rate for 10 E. coli O157:H7 strains suspended in 10:1 SGF-CGB was -0.081 +/- 0.068, a rate that was 12-fold lower than that observed for SGF-saline. In comparison, the average inactivation rate for Shigella flexneri strain 5348 in 100:1 and 10:1 SGF-saline was -8.784 and -17.310, respectively. These latter inactivation rates were 7- to 17-fold higher than those for E. coli O157:H7 strains in SGF-saline and were 4-fold higher than those for E. coli O157:H7 strains in SGF-CGB. The survival rate of E. coli O157:H7 strain GFP80EC increased as the dose of antacid increased from one-half to twice the prescribed dose. A similar trend was observed for the matrix pH over the range of pH 1.6 to 5.7, indicating that pH is a primary factor affecting E. coli O157:H7 survival in SGF-CGB+A. These results can be used in risk assessment to define dose-response relationships for E. coli O157:H7 and to evaluate potential surrogate organisms.

Rabeprazole improves and maintains overall well being in gastroesophageal reflux disease (GERD) over 5 years

Purpose: To compare the impact on overall physical well being of rabepmzole 20 rag, rabeprazole 10 mg, and placebo over 5 years of mainter~ance therapy in GERD patients. Methods: 497 patients, previously diagnosed with erosive/ulcerative GERD healed in an acute efficacy trial, entered a multicenter, double-blind, placebo-controlled, parallel-arm, 1year maintenance study. All patients completing 1 year without GERD relapse were eligible to participate for 4 more years in an extension phase. Efficacy variables of the combined 5 years (260 weeks) of study included: overall physical well-being score (scale, 0 = very good; 4 = very poor), relapse of seventy/frequency of daytime and nighttime heartburn, and antacid use. Results: At endpoint (260 weeks), both rabeprazole groups had significantly higher ratings in overall well being versus placebo (p 2; p-<0.008). Rabeprazole 20 mg also produced a significantly lower relapse rate than rabeprazole 10 mg for weeks 4-65 (p~0.038). These results in overall well being corresponded with significantly lower relapse rates with rabeprazole versus placebo in heartburn frequency and severity seen over 5 years (p-<0.02). Mean daily antacid dose consumed by the rabeprazole 20 mg group (0.17) was less than in the rabeprazole 10 mg (0.24) or placebo groups (0.24) at endpoint. For weeks 4-104 and week 143, there were significant differences in change in daily antacid use from baseline favoring both rabeprazole groups versus the placebo group (p-<0.05). Conclusions: 5-year maintenance therapy with rabeprazole improves overall well being compared with placebo. Research supported by Eisai Inc., Teaneck, NJ and Janssen Pharmaceutica Inc., Titusville, NJ.

Short course acid suppressive treatment for patients with functional dyspepsia: results depend onHelicobacter pyloristatus

BACKGROUND AND AIMSTreatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence ofHelicobacter pylori infection influences the response.METHODSAfter a complete diagnostic workup, 792...

Integrated acidity: a novel technique demonstrating synergy between low dose ranitidine and antacid for acid reduction and relief of meal-induced heartburn

Integrated acidity: a novel technique demonstrating synergy between low dose ranitidine and antacid for acid reduction and relief of meal-induced heartburn

Effects of Amino Acid Dialysis Solution on the Nutrition of Continuous Ambulatory Peritoneal Dialysis Patients

To evaluate the influence of 1.1% amino acid dialysis solution (AADS) on parameters of nutrition in continuous ambulatory peritoneal dialysis (CAPD) patients. Studies were performed in 8 men, using AADS for the overnight exchange. Before starting AADS, food intake, nutritional status, and laboratory indices were evaluated and compared to the respective parameters obtained after 3 and 6 months of treatment with AADS, as well as after 3 months of AADS withdrawal. With the start of AADS, doses of antacids were increased and modified during AADS administration; the modified doses were continued through 3 months after cessation of AADS. Another group of CAPD patients using standard dialysis solutions served as controls. In these patients the same parameters were evaluated four times at 3-month intervals. Administration of AADS resulted in: (1) 91% absorption of amino acids and improvement of serum amino acid pattern; (2) no change in nutritional intake during the treatment, but after the 3 months of AADS therapy, levels of nutrient intake were lower than those 3 months after withdrawal of AADS with correction of metabolic acidosis; (3) no change in indices of nutritional status, but 3 months after AADS discontinuation, total body weight, lean body mass, and body mass index were significantly higher than those shown after 3 months of treatment; (4) an increase in hemoglobin concentration, hematocrit, BUN, and blood H+. The examined parameters were not significantly changed in patients treated for 9 months with standard dialysis solutions exclusively. The values of nitrogen balance obtained during AADS administration and after 3 months of AADS withdrawal were significantly higher than those obtained in the respective periods in the control group. The blood pH, pCO2, and HCO3- in the last period of the study were higher in the AADS group than in the control group. In relatively well-nourished CAPD patients, overnight AADS administration results in increased serum concentration of amino acids without changes in other nutritional parameters. The use of AADS should be associated with increased doses of antacid medication, which abolishes the metabolic effects of acidosis that develop during AADS administration and facilitates positive nitrogen balance.

Pharmacokinetics and pharmacodynamics of fluoroquinolones

'Division of Clinical Pharmacology, Department of Medicine, Albany Medical College, Albany, New York, USA; 21NSERM U479, Service d'Hematologie et d'Immunologie Biologiques, CHU Xavier BICHAT, Paris, France; 3Department of Infectious Diseases, Uppsala University Hospital, Uppsala, Sweden; 4Hoechst Marion Roussel Inc, Bridgewater, New Jersey, USA; 5Med Klinik 111, Frankfurt a m Main, Germany; 61nstitute for Biomedical & Pharmaceutical Research, Nurnberg Herodsberg, Germany; 7Hoechst Marion Roussel AG, Clinical Development, Frankfurt a m Main, Germany

Central peptidergic control of gastric acid secretion.

The effect of a low dose antacid treatment on mucosal prostaglandin metabolism was studied in 15 healthy volunteers. A daily dose of 46 mmol (= 138 mval) Al(OH)3 and 42 mmol (= 84 mval) Mg(OH)2 with a titrated in vitro neutralising capacity of 272 mval of H+ was given for three weeks. Total prostaglandin formation and the prostaglandin profile as well as the degradation of PGE2 were assayed by incubating homogenates of endoscopic biopsies from antral and duodenal mucosa with the precursor (14C)arachidonic acid. Total prostaglandin synthesis in antrum (623 (110) pmol/mg protein) and duodenum (432 (72) pmol/mg) was stimulated after three weeks administration of low dose antacids by 176% (p less than 0.05) and 154% (p less than 0.05), respectively. An untreated control group exhibited no significant changes. In contrast, the prostaglandin profile showed only a small increase of the prostacyclin metabolite 6-keto PGF1a (p less than 0.05) at the expense PGD2. PGE2 catabolism was unaffected. This enhanced activity of mucosal prostaglandin cyclooxygenase might represent one possible mechanism of action of a low dose antacid treatment.

Comparative Effects of Liquid Antacids on Esophageal and Gastric pH in Patients with Heartburn.

This double-blind crossover trial compared the postmeal effects of single doses of liquid antacids on esophageal and gastric pH in patients with a history of heartburn. Treatment consisted of one of two antacids containing the same active components---aluminum and magnesium hydroxide---but different in vitro acid-neutralizing capacities (ANCs). The pH was assessed continually from 1 h before a refluxogenic meal to 4 h after its completion in 24 subjects who received 20 ml of Mylanta((R)) Double Strength (MYL-20: ANC = 101.6 mEq), 20 or 30 ml of Extra-Strength Maalox((R)) Plus (MA-20, MA-30: ANC = 116.2 and 174.3 mEq, respectively), or placebo (ANC = 0) in random order. Esophageal pH increased rapidly and significantly (p < 0.05) to peak values of 7.0--7.4 with antacid. The increase in mean esophageal pH values was significantly higher (p < 0.05) than placebo for 30 min with MA-20 and for at least 70 min with MYL-20 and MA-30. In contrast, gastric pH rose slowly to mean peaks of 2.9--3.1 with antacid. During this interval, only MYL-20 was associated with significant improvements (p < 0.05 versus placebo) in total number of reflux episodes and total time that esophageal pH measured >4. Thus, ANC alone is not a useful guide in predicting in vivo antacid behavior, as in this study where the antacid dose with the lowest ANC demonstrated a duration of action as long or longer than that of antacid doses with higher ANC values. The rapid, prolonged increases in esophageal pH that preceded modest changes in gastric pH strongly suggest that the lower esophagus is the primary site of antacid action for heartburn relief.