Pharmacokinetics of gatifloxacin and interaction with an antacid containing aluminum and magnesium.
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The pharmacokinetics of gatifloxacin (400 mg orally) and the influence of the antacid aluminum magnesium hydroxide (20 ml of Maalox 70) on the bioavailability of gatifloxacin in 24 healthy volunteers were assessed. In an open, randomized, six-period crossover study, the volunteers received either gatifloxacin alone (treatments A and D); aluminum magnesium hydroxide concomitant with gatifloxacin (treatment C); or aluminum magnesium hydroxide 2 h before (treatment B), 2 h after (treatment E), or 4 h after gatifloxacin administration (treatment F). Gatifloxacin concentrations were measured by a validated bioassay and high-performance liquid chromatography. Pharmacokinetics of a single 400-mg dose of gatifloxacin alone were characterized as follows (mean +/- standard deviation): peak concentration (Cmax), 3.8 +/- 0. 5 (treatment A) and 3.4 +/- 0.9 (treatment D) microgram/ml; time to Cmax, 1.4 +/- 0.8 (treatment A) and 1.7 +/- 0.7 (treatment D) h; area under the curve from time zero to infinity (AUC0-infinity), 33. 5 +/- 5.9 (treatment A) and 31.4 +/- 3.4 (treatment D) microgram. h/ml; urine recovery, (83 +/- 6)% (treatment A) and (84 +/- 8)% (treatment D). Comparison of the results obtained by bioassay showed a good correlation. Aluminum magnesium hydroxide administration 2 h before (treatment B) or concomitant with (treatment C) gatifloxacin decreased the Cmax by 45% (2.1 +/- 1.2 microgram/ml) or even 68% (1.2 +/- 0.4 microgram/ml) highly significantly (P < 0.01). AUC0-infinity was significantly reduced from 33.5 +/- 5.9 to 19.4 +/- 6.9 microgram. h/ml (by 42%) or even to 11.9 +/- 3.3 microgram. h/ml (by 64%) (P < 0. 01). If aluminum magnesium hydroxide was given 2 h after gatifloxacin (treatment E), there was no significant reduction of concentration in serum but AUC0-infinity was significantly reduced from 31.4 +/- 3.4 to 25.9 +/- 5.3 microgram. h/ml (18%) (P < 0.01). Aluminum magnesium hydroxide given 4 h after gatifloxacin (treatment F) showed no influence on the gatifloxacin pharmacokinetics. Therefore, the optimal time between gatifloxacin application and the intake of an aluminum-containing antacid should be 4 h. (+info)
Onset of action during on-demand treatment with maalox suspension or low-dose ranitidine for heartburn.
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AIM: To compare the onset of action of the local antacid Maalox and the systemic H2-antagonist ranitidine, during 'on demand' ambulant treatment of a single heartburn episode, using a randomized, parallel group, double-blind, double-dummy design. METHODS: Subjects with self-perceived heartburn without known gastrointestinal disease or interfering treatments were selected with questionnaires. The study was performed unsupervised, whenever heartburn required medication. An electronic patient diary gave instructions when to take study medication, and provided visual analogue scales and five-item relief ratings for heartburn, at frequent time intervals activated by an alarm-clock. RESULTS: After a study of the natural history of heartburn and the feasibility of the study procedures in 23 patients, 49 subjects took Maalox and 45 ranitidine. Half of these experienced meaningful heartburn relief within 19 min after Maalox, and within 70 min after ranitidine. One hour after intake, the average heartburn relief score was 3.43 in the Maalox group and 3.04 in the ranitidine group (3 means 'slight improvement' and 4 'strong improvement'). Heartburn was similar in both groups after 3 h. CONCLUSIONS: Maalox provides faster relief of heartburn than ranitidine. Heartburn can be assessed frequently and reliably under ambulant conditions using an electronic patient diary. (+info)
The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation.
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AIMS: To determine whether magnesium given orally decreases the recurrence rate of atrial fibrillation after elective direct current cardioversion of persistent atrial fibrillation. METHODS AND RESULTS: Consecutive outpatients were randomized to treatment with oral magnesium (10.3 mmol) or placebo twice daily in a double-blind fashion. Two groups were studied; magnesium study: 170 patients with atrial fibrillation persistent for >1 month, scheduled for their first direct current cardioversion. No concomitant antiarrhythmic drugs of class I or III were allowed. Sotalol and magnesium study: 131 patients with recurrence of persistent atrial fibrillation after previous direct current cardioversion, or a history of paroxysmal atrial fibrillation, treated with sotalol. Patients were followed until recurrence of atrial fibrillation or for at least 6 months. Magnesium study: at cardioversion 67 of 85 (79%) in the placebo group and 64 of 85 (75%) in the magnesium group had converted to sinus rhythm. At the end of the study, with a follow-up of 6 to 42 months, 15% of patients in the placebo group and 19% of patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.37). Sotalol and magnesium study: pharmacological conversion to sinus rhythm, after oral treatment, was achieved in 34 of 131 (26%) patients. Sinus rhythm, with or without cardioversion, was restored in 89% and 85% of the patients in the placebo and magnesium groups, respectively. At the end of the study, with a follow-up of 6 to 42 months, 37% of patients in the placebo group and 30% of patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.64). CONCLUSION: In patients with persistent atrial fibrillation, oral treatment with magnesium alone or as an adjuvant to sotalol, does not influence the recurrence rate of atrial fibrillation after elective cardioversion. (+info)
The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.
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AIMS: To examine the effect of concomitant cimetidine or antacid administration on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers in two open-label, randomized studies. METHODS: The first study was a parallel-group design in which 22 healthy male volunteers received sildenafil (50 mg) on days 1 and 5 and cimetidine (800 mg) or placebo on days 3, 4, 5, and 6. Blood samples were collected predose and at specified times up to 48 h postdose on days 1 and 5 to determine plasma levels of sildenafil and its metabolite, UK-103,320. The second study was a two-way crossover design in which 12 volunteers received sildenafil with or without a 30-ml dose of a magnesium hydroxide/aluminium hydroxide antacid. Blood samples were collected and analysed as in the first study. The two study periods were separated by at least 14 days. RESULTS: Coadministration of cimetidine had no statistically significant effect on the tmax or kel of sildenafil but caused a statistically significant increase in sildenafil AUCt and Cmax of 56% and 54%, respectively (P<0.01). Differences between the two treatment groups were smaller for the metabolite than for sildenafil, although cimetidine treatment did significantly (P<0.05) increase the AUCt for UK-103,320 by 30%. Antacid coadministration had no statistically significant effect on any pharmacokinetic parameter of sildenafil or UK-103,320. Whether taken alone, with cimetidine, or with an antacid, sildenafil was well tolerated. Most adverse events were mild in nature, and no subject withdrew from either study for any reason related to the drug. CONCLUSIONS: Cimetidine co-administration produced an increase in sildenafil plasma levels; however, this increase is not sufficient to warrant dosage adjustment of either drug. Antacid coadministration had no effect on the pharmacokinetic profile of sildenafil. (+info)
Lack of pharmacokinetic interaction between the oral anti-influenza neuraminidase inhibitor prodrug oseltamivir and antacids.
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AIMS: Oseltamivir is an oral ester prodrug of its active metabolite Ro 64-0802, a potent and selective neuraminidase inhibitor of the influenza virus. The object of this study was to evaluate whether the oral absorption of oseltamivir was reduced in the presence of two main classes of antacid, Maalox(R) suspension (containing magnesium hydroxide and aluminium hydroxide) and Titralac(R) tablets (containing calcium carbonate). METHODS: Twelve healthy volunteers completed a randomized, single dose, three-period crossover study. Each volunteer received in a fasted state, 150 mg oseltamivir alone (Treatment A), 150 mg oseltamivir with a 20 ml Maalox suspension (Treatment B), and 150 mg oseltamivir with four Titralac tablets (Treatment C), with 7-10 days washout in between treatments. Plasma and urine concentrations of oseltamivir and Ro 64-0802 were measured using a validated h.p.l.c./MS/MS assay. Pharmacokinetic parameters were calculated for oseltamivir and Ro 64-0802. Since antacids are locally acting drugs and generally not expected to be absorbed substantially into the systemic system, no plasma or urine concentrations of antacids were measured. RESULTS: Bioequivalence was achieved for the primary pharmacokinetic parameters Cmax and AUC(0, infinity ) of Ro 64-0802 following administration of oseltamivir with either Maalox suspension or Titralac(R) tablets vs administration of oseltamivir alone. The bioavailability (90% confidence intervals) of Ro 64-0802 following administration of oseltamivir together with Maalox suspension vs administration of oseltamivir alone, was 90% (83.6, 96.9%) for C(max) and 94.1% (91.4, 96.9%) for AUC(0, infinity); similarly, for Titralac tablets, the equivalent values were 95.1% (88.3, 102%) for C(max) and 94.7% (91.9, 97.5%) for AUC(0, infinity). CONCLUSIONS: The coadministration of either Maalox suspension or Titralac tablets with oseltamivir has no effect on the pharmacokinetics of either oseltamivir or Ro 64-0802, and conversely, there is no evidence that coadministration with oseltamivir has an effect on the safety and tolerability of either Maalox suspension or Titralac tablets. There was no pharmacokinetic interaction between oseltamivir with either antacid, demonstrating that the oral absorption of oseltamivir was not impaired in the presence of antacids containing magnesium, aluminium or calcium. (+info)
Pantoprazole maintenance therapy prevents relapse of erosive oesophagitis.
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OBJECTIVES: To compare the safety and efficacy of pantoprazole with ranitidine for the maintenance of endoscopically documented healed (grade 0 or 1) erosive oesophagitis. METHODS: Patients (371) were randomly assigned to receive pantoprazole 10, 20 or 40 mg or ranitidine 150 mg. Endoscopies were performed after 1, 3, 6 and 12 months or when symptoms suggesting relapse (grade = 2) developed. Gastric biopsies were obtained at baseline and on at least one postbaseline visit. Symptom-free days and Gelusil use were assessed. RESULTS: Pantoprazole was significantly (P < 0.001) more effective in maintaining erosive oesophagitis healing. After 12 months, 33%, 40%, 68% and 82% of patients remained healed for the ranitidine and pantoprazole 10, 20 and 40 mg groups, respectively. Daytime and night-time heartburn were eliminated in > 90% of days for the pantoprazole 40 mg group. Gelusil use was significantly lower with pantoprazole 20 and 40 mg than with ranitidine (P < 0.02) during the first 9 months. CONCLUSIONS: Twelve months of maintenance therapy with pantoprazole (10-40 mg once daily) was superior to ranitidine (150 mg twice daily) in maintaining erosive oesophagitis healing. Pantoprazole 40 mg provided the most consistent efficacy and was well tolerated. (+info)
Preventive effect of hydrotalcite on gastric mucosal injury in rats induced by taurocholate.
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AIM: To study the preventive effect of hydrotalcite on gastric mucosal injury in rat induced by taurocholate, and to investigate the relationship between the protective mechanism of hydrotalcite and the expression of trefoil factor family 2 (TFF2) mRNA and c-fos protein. METHODS: Forty five male Wistar rats were randomly divided into hydrotalcite group, ranitidine group and control group. Gastric mucosal injury was induced by introgastric acidified taurocholate. OD value of TFF2 mRNA expression in gastric mucous cells was determined by hybridization and computer image analysis system. OD value of c-fos protein expression in gastric mucous cells was measured by immunohistochemistry and computer image analysis system. RESULTS: The gross mucosal injury index in hydrotalcite group was significantly lower than that in ranitidine group and control group (8.60+/-2.20 vs 16.32+/-4.27, 29.53+/-5.39; P<0.05, P<0.01). The expression level of TFF2 mRNA in hydrotalcite group was markedly higher than that in ranitidine group and control group (0.56+/-0.09 vs 0.30+/-0.05, 0.28+/-0.03, P<0.05). The OD value of c-fos protein in hydrotalcite group was higher than that in ranitidine group and control group (0.52+/-0.07 vs 0.31+/-0.04, 0.32+/-0.05, P<0.05). CONCLUSION: Hydrotalcite can protect gastric mucosal injury in rats induced by taurocholate, which may be related to the increased expression of TFF2 and c-fos protein. (+info)
Intercalation compounds of hydrotalcite-like anionic clays with anti-inflammatory agents, II: Uptake of diclofenac for a controlled release formulation.
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The purpose of this study was to investigate whether hydrotalcite is able to intercalate diclofenac, a nonsteroidal anti-inflammatory drug, and release it in a controlled manner. Layered Mg-Al hydrotalcite in the chloride form was used as a host, and the intercalation compound was prepared by Cl-/diclofenac anionic exchange. Drug release from the intercalation compound was performed in vitro in simulated intestinal fluid at pH 7.5 according to USP 24 and in a pH 7.0 solution designed to mimic the ionic conditions of the small intestine. Results from the intercalation process show that hydrotalcite is able to intercalate diclofenac with a simple procedure and with a good drug loading (55% wt/wt). The in vitro drug release was remarkably lower than that from the corresponding physical mixture at both pH 7.5 and pH 7.0. In the latter case, the release was not complete at 24 hours. The kinetic analysis shows the importance of the diffusion through the particle in controlling the drug release rate. The obtained results show that hydrotalcite may be used to prepare modified release formulations. (+info)