-
Antimicrobial Agents and Chemotherapy Apr 2023Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label,... (Clinical Trial)
Clinical Trial
Effect of an Antacid (Aluminum Hydroxide/Magnesium Hydroxide/Simethicone) or a Proton Pump Inhibitor (Omeprazole) on the Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Adult Subjects.
Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets). In Period 2, subjects received a single oral dose of aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension co-administered with a single dose of TBP-PI-HBr 600 mg. In Period 3, subjects received a single oral dose of omeprazole 40 mg once daily over 5 days, followed by single dose administration of TBP-PI-HBr 600 mg on day 5. In each period, whole blood samples were obtained prior to, and up to 24 h, following TBP-PI-HBr dose administration in order to characterize TBP PK. A 7-day washout was required between periods. Twenty subjects were enrolled and completed the study. Following co-administration of TBP-PI-HBr with either aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole, total TBP exposure (area under the curve [AUC]) was approximately 11% (geometric mean ratio 89.2, 90% confidence interval: 83,2, 95.7) lower, and Cmax was 22% (geometric mean ratio 78.4, 90% confidence interval: 67.9, 90.6) and 43% (geometric mean ratio 56.9, 90% confidence interval: 49.2, 65.8) lower, respectively, compared to administration of TBP-PI-HBr alone. Mean TBP elimination half-life (t) was generally comparable across treatments (range: 1.0 to 1.5 h). Concomitant administration of TBP-PI-HBr with omeprazole or aluminum hydroxide/magnesium hydroxide/simethicone is not expected to impact the efficacy of TBP-PI-HBr, as there is minimal impact on TBP plasma AUC, which is the pharmacodynamic driver of efficacy. Co-administration was generally safe and well tolerated.
Topics: Adult; Humans; Administration, Oral; Aluminum Hydroxide; Antacids; Anti-Ulcer Agents; Cross-Over Studies; Drug Interactions; Magnesium Hydroxide; Omeprazole; Proton Pump Inhibitors; Simethicone
PubMed: 36943038
DOI: 10.1128/aac.01495-22 -
Journal of Colloid and Interface Science Feb 2022Enhancing the interfacial dispersion and suspension stability is crucial for magnesium hydroxide (Mg(OH)) nanomaterials in the long-term deacidification of paper-based...
Colloidal magnesium hydroxide Nanoflake: One-Step Surfactant-Assisted preparation and Paper-Based relics protection with Long-Term Anti-Acidification and Flame-Retardancy.
Enhancing the interfacial dispersion and suspension stability is crucial for magnesium hydroxide (Mg(OH)) nanomaterials in the long-term deacidification of paper-based cultural relics. However, because of the low specific surface area and the poor solvent compatibility of as-prepared large-sized Mg(OH), it often tends to agglomerate and settle down during the usage and storage, that is harmful for paper protection due to its unevenly deacidification and nonuniformly distribution on paper cellulose. Herein, we propose a feasible preparation of colloidal Mg(OH) ultrathin nanoflakes with high dispersion stability via a simple one-step surfactant-assisted strategy. The surfactant acts as both a structure-direct agent to confine the growth of Mg(OH) with rich active sites and a surface modifier to enhance its solvent adaptability and dispersion stability, avoiding the common fussy procedure with additional steric stabilizer. Owing to the evenly interaction with free acid species therein and the uniformly distribution on the paper fiber as alkaline reserve, the as-obtained Mg(OH) presents the superior paper protection performance characterized by its safer pH of 7.29 for the original aged paper (pH = 5.03) and the excellent long-term anti-acidification effect with competitive pH of 5.47 after accelerated-aging at 105 °C for 5 months. Furthermore, Mg(OH) nanoflakes with surfactant-modified structure also endue them as an improved flame retardant for multifunctional paper protection. The protection with Mg(OH) has little effect on the paper surface properties and cellulose crystallinity, in line with the principle of least intervention. This work will put forward a feasible way toward colloidal Mg(OH) nanoflakes with excellent paper protection performance, shedding light on the development of emerging protection materials for paper-based cultural relics.
Topics: Cellulose; Flame Retardants; Magnesium Hydroxide; Nanostructures; Surface-Active Agents
PubMed: 34571317
DOI: 10.1016/j.jcis.2021.09.041 -
ACS Applied Materials & Interfaces Jun 2021Magnesium hydroxide (Mg(OH)) is hailed as a cheap and biocompatible material with antimicrobial potential; however, research aimed at instilling additional properties...
Magnesium hydroxide (Mg(OH)) is hailed as a cheap and biocompatible material with antimicrobial potential; however, research aimed at instilling additional properties and functionality to this material is scarce. In this work, we synthesized novel, fluorescent magnesium hydroxide nanosheets (Mg(OH)-NS) with a morphology that closely resembles that of graphene oxide. These multifunctional nanosheets were employed as a potent antimicrobial agent against several medically relevant bacterial and fungal species, particularly on solid surfaces. Their strong fluorescence signature correlates to their hydroxide makeup and can therefore be used to assess their degradation and functional antimicrobial capacity. Furthermore, their pH-responsive change in fluorescence can potentially act as a pH probe for wound acidification, which is characteristic of healthy wound healing. These fluorescent antimicrobial nanosheets were stably integrated into biocompatible electrospun fibers and agarose gels to add functionality to the material. This reinforces the suitability of the material to be used as antimicrobial bandages and gels. The biocompatibility of the Mg(OH)-NS for topical medical applications was supported by its noncytotoxic action on human keratinocyte (HaCaT) cells.
Topics: Anti-Bacterial Agents; Antifungal Agents; Bandages; Candida; Candida albicans; Escherichia coli; Fluorescence; HaCaT Cells; Humans; Hydrogen-Ion Concentration; Magnesium Hydroxide; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nanostructures
PubMed: 34105937
DOI: 10.1021/acsami.1c05908 -
Journal of Colloid and Interface Science Aug 2008Well-dispersed magnesium hydroxide nanoplatelets were synthesized by a simple water-in-oil (w/o) microemulsion process, blowing gaseous ammonia (NH(3)) into...
Well-dispersed magnesium hydroxide nanoplatelets were synthesized by a simple water-in-oil (w/o) microemulsion process, blowing gaseous ammonia (NH(3)) into microemulsion zones solubilized by magnesium chloride solution (MgCl(2)). Typical quaternary microemulsions of Triton X-100/cyclohexane/n-hexanol/water were used as space-confining microreactors for the nucleation, growth, and crystallization of magnesium hydroxide nanoparticles. The obtained magnesium hydroxide was characterized by field-emission scanning electron microscopy (FESEM), high-resolution transmission election microscopy (HRTEM), X-ray powder diffraction (XRD), laser light scattering, Fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis-differential scanning calorimetry (TGA-DSC). The mole ratio of water to surfactant (omega(0)) played an important role in the sizes of micelles and nanoparticles, increasing with the increase of omega(0). The compatibility and dispersibility of nanoparticles obtained from reverse micelles were improved in the organic phase.
Topics: Cyclohexanes; Emulsions; Hexanols; Magnesium Hydroxide; Micelles; Nanostructures; Octoxynol; Water
PubMed: 18511061
DOI: 10.1016/j.jcis.2008.03.052 -
Basic & Clinical Pharmacology &... Mar 2017Despite the presumption of a beneficial effect of magnesium (Mg) supplementation on various diseases, little is known concerning the pharmacokinetics of Mg hydroxide.... (Clinical Trial)
Clinical Trial
Despite the presumption of a beneficial effect of magnesium (Mg) supplementation on various diseases, little is known concerning the pharmacokinetics of Mg hydroxide. This study was designed to provide a pharmacokinetic profile of Mg hydroxide after a single oral dose. Ten healthy male adults participated in this cross-over study with three 24-hr study days. Interventions were (i) none (baseline), (ii) oral intake of three (3 × 360 mg) tablets of Mg hydroxide (Mablet ) and (iii) IV bolus infusion of 2 g Mg sulphate (index drug). Blood samples were collected before the single dose, after (i.e. after treatment administration) 15, 30, 60, 90 and 120 min. and after 3, 4, 6, 8, 12 and 24 hr. Urine was collected in four 6-hr periods per study day. Blood (N = 10) and urine (N = 6) Mg were analysed by descriptive statistics. Bioavailability was 14.9% (CI: 8.3; 26.8), blood clearance was 5.1 L/hr (CI: 2.1; 17.0), apparent volume of distribution was 60.2 L (CI: 35.6; 102.0), elimination constant was 0.08 per hour (CI: 0.05; 0.14), half-life was 8.3 hr (CI: 4.8; 14.1), C was 0.11 mmol/L (CI: 0.07; 0.14), and AUC was 92.3 mmol/L × min. (CI: 45.5; 139.1). Urine Mg excretion augmented by 17.7% (CI: 8.9; 35.0) from baseline. No severe side effects were observed. The bioavailability of Mg hydroxide was 15%, and it constitutes a clinically relevant option for oral Mg supplementation. No severe side effects were seen.
Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Half-Life; Healthy Volunteers; Humans; Infusions, Intravenous; Magnesium Hydroxide; Male; Young Adult
PubMed: 27412366
DOI: 10.1111/bcpt.12642 -
Revista de Gastroenterologia de Mexico... 2023There are few studies that compare polyethylene glycol (PEG) 3350 and magnesium hydroxide (MH), as long-term treatment of functional constipation (FC) in children, and... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy, safety, and acceptability of polyethylene glycol 3350 without electrolytes vs magnesium hydroxide in functional constipation in children from six months to eighteen years of age: A controlled clinical trial.
INTRODUCTION AND AIMS
There are few studies that compare polyethylene glycol (PEG) 3350 and magnesium hydroxide (MH), as long-term treatment of functional constipation (FC) in children, and they do not include infants as young as 6 months of age. Our aim was to determine the efficacy, safety, and acceptability of PEG vs MH in FC, in the long term, in pediatric patients.
METHODS
An open-label, parallel, controlled clinical trial was conducted on patients from 6 months to 18 years of age, diagnosed with FC, that were randomly assigned to receive PEG 3350 or MH for 12 months. Success was defined as: ≥ 3 bowel movements/week, with no fecal incontinence, fecal impaction, abdominal pain, or the need for another laxative. We compared adverse events and acceptability, measured as rejected doses of the laxative during the study, in each group and subgroup.
RESULTS
Eighty-three patients with FC were included. There were no differences in success between groups (40/41 PEG vs 40/42 MH, p = 0.616). There were no differences in acceptability between groups, but a statistically significant higher number of patients rejected MH in the subgroups > 4 to 12 years and > 12 to 18 years of age (P = .037 and P = .020, respectively). There were no differences regarding adverse events between the two groups and no severe clinical or biochemical adverse events were registered.
CONCLUSIONS
The two laxatives were equally effective and safe for treating FC in children from 0.5 to 18 years of age. Acceptance was better for PEG 3350 than for MH in patients above 4 years of age. MH can be considered first-line treatment for FC in children under 4 years of age.
Topics: Humans; Child; Child, Preschool; Laxatives; Magnesium Hydroxide; Treatment Outcome; Polyethylene Glycols; Constipation; Electrolytes
PubMed: 34961695
DOI: 10.1016/j.rgmxen.2021.12.005 -
Journal of Toxicology. Clinical... 1991This 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... (Review)
Review
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.
Topics: Administration, Oral; Calcium Gluconate; Cathartics; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Magnesium Hydroxide; Potassium Chloride
PubMed: 2051509
DOI: 10.3109/15563659109038614 -
The New England Journal of Medicine Apr 1991There is no specific method of diagnosing magnesium-induced diarrhea. Therefore, the frequency and clinical importance of diarrhea caused by magnesium are unknown. The... (Clinical Trial)
Clinical Trial
BACKGROUND
There is no specific method of diagnosing magnesium-induced diarrhea. Therefore, the frequency and clinical importance of diarrhea caused by magnesium are unknown. The purposes of this study were to establish a method for diagnosing magnesium-induced diarrhea and to apply it to patients with chronic diarrhea.
METHODS
We measured fecal output of soluble magnesium and fecal magnesium concentration in 19 normal subjects with formed stools (15 collection periods), with non-magnesium-induced diarrhea (36 collection periods), and with diarrhea induced by magnesium hydroxide alone (11 collection periods) or in combination with phenolphthalein (3 collection periods), and in 359 patients with chronic diarrhea.
RESULTS
The upper limits of fecal output of soluble magnesium and fecal magnesium concentration in normal subjects were 14.6 mmol per day and 45.2 mmol per liter, respectively. When normal subjects had diarrhea due to the ingestion of magnesium hydroxide alone or in combination with phenolphthalein, fecal magnesium output was always abnormally high. For each millimole increase in fecal magnesium output, fecal weight increased by approximately 7.3 g. The fecal magnesium concentration was very high when magnesium was the only cause of diarrhea but only moderately elevated when diarrhea was induced by magnesium hydroxide plus phenolphthalein. Biochemical and clinical evidence indicated that excessive ingestion of magnesium was an important cause of chronic diarrhea in 15 of the 359 patients with chronic diarrhea (4.2 percent), if not the only cause.
CONCLUSIONS
Quantitative fecal analysis for soluble magnesium is an accurate method of diagnosing magnesium-induced diarrhea. Some patients with chronic diarrhea ingest excessive amounts of magnesium (in antacids or food supplements), and physicians may fail to discover this before embarking on an expensive and invasive diagnostic evaluation.
Topics: Adult; Aged; Child; Chronic Disease; Diarrhea; Drug Overdose; Feces; Female; Humans; Magnesium; Magnesium Hydroxide; Male; Middle Aged; Phenolphthalein; Phenolphthaleins; Reference Values
PubMed: 2005938
DOI: 10.1056/NEJM199104113241502 -
Magnesium Research Jun 2005Critically evaluate the experimental evidence and clinical trial outcomes as the basis for use of magnesium (Mg) supplements as therapy for calcium oxalate... (Review)
Review
PURPOSE
Critically evaluate the experimental evidence and clinical trial outcomes as the basis for use of magnesium (Mg) supplements as therapy for calcium oxalate nephrolithiasis.
MATERIALS AND METHODS
Literature search of MedLine and Web of Science through January 2005; articles cited in papers found by searches.
RESULTS
Magnesium inhibits calcium oxalate crystallization in human urine and model systems. Magnesium also inhibits absorption of dietary oxalate from the gut lumen. Three early trials of Mg oxide (MgO) and Mg hydroxide (Mg(OH)2) reported lower rates of recurrent stone formation. However in a double-blind, randomized, placebo-controlled trial with more carefully selected patients, there was no significant difference between recurrence rates with 650 or 1300 mg MgO daily and the placebo. Another trial reported 391 mg (21 meq) Mg daily as a mixed salt, Mg potassium citrate, reduced calcium stone recurrence by 90%, similar to potassium citrate, but with better gastrointestinal tolerance. The failure of MgO and Mg(OH)2 as sole therapy may be related to poor absorption and low rates of Mg deficiency in the patient populations tested.
CONCLUSIONS
Clinical trial evidence does not justify the use of MgO or Mg(OH)2 as a sole therapy for calcium oxalate kidney stones in a general patient population. However, the addition of magnesium to potassium citrate therapy improves outcomes. Clinical trials should focus on patients who are likely to be Mg deficient.
Topics: Calcium Oxalate; Clinical Trials as Topic; Crystallization; Humans; Kidney Calculi; Magnesium; Magnesium Hydroxide; Magnesium Oxide
PubMed: 16100850
DOI: No ID Found -
ACS Nano Jul 2018Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts...
Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts resulting from degradation can generate vigorous inflammatory reactions, often leading to clinical failure. We present an approach to prevent acid-induced inflammatory responses associated with biodegradable polymers, here poly(lactide- co-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)) nanoparticles, which neutralize the acidic environment. In particular, we demonstrated that incorporating the modified Mg(OH) nanoparticles within degradable coatings on drug-eluting arterial stents efficiently attenuates the inflammatory response and in-stent intimal thickening by more than 97 and 60%, respectively, in the porcine coronary artery, compared with that of drug-eluting stent control. We also observed that decreased inflammation allows better reconstruction of mouse renal glomeruli in a kidney tissue regeneration model. Such modified Mg(OH) nanoparticles may be useful to extend the applicability and improve clinical success of biodegradable devices used in various biomedical fields.
Topics: Animals; Cell Survival; Cells, Cultured; Drug-Eluting Stents; Humans; Inflammation; Magnesium Hydroxide; Mice; Nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer; U937 Cells
PubMed: 29812907
DOI: 10.1021/acsnano.8b02365