-
BMC Cancer Apr 2022Saline hydration with addition of mannitol have commonly been the strategy to avoid cisplatin induced acute kidney injury (AKI). While the initial reports demonstrated...
BACKGROUND
Saline hydration with addition of mannitol have commonly been the strategy to avoid cisplatin induced acute kidney injury (AKI). While the initial reports demonstrated that mannitol diuresis decreased cisplatin induced renal injury, others have shown renal injury to be worsened.
OBJECTIVE
To compare the risk of AKI in cancer patients receiving high dose cisplatin with and without addition of mannitol.
METHOD
This was an ambispective cohort study based on consecutive sampling at Cipto Mangunkusumo General Hospital (CMGH) and Mochtar Riady Comprehensive Cancer Centre (MRCCC) Siloam Hospitals. The data was obtained from September 2017 to February 2018. The choice of mannitol administration based on attending physician clinical judgement. The primary outcome was increase of serum creatinine more than 0.3 mg/dL or 1.5 times from baseline. Analysis was done by using univariate, bivariate and multivariate logistic regression to obtain crude risk ratio and adjusted risk ratio of cisplatin induced AKI probability caused by mannitol addition on top of usual saline hydration protocol.
RESULT
Data from 110 patients (57.3% male) with a median age of 44.5 years (range 19 to 60 years) were collected; 63 received saline with the addition of mannitol and 47 received saline only. Incidence of AKI were higher in mannitol vs saline only group. Bivariate analysis showed higher probability of post chemotherapy AKI in mannitol group, however it was statistically insignificant (RR 2.168; 95% CI 0.839-5.6; p = 0.094). On multivariate analysis the age adjusted RR was 2.852 (95% CI 0.68-11.96; p = 0.152).
CONCLUSION
The addition of mannitol to hydration did not reduce the risk of cisplatin induced AKI as compared with saline hydration only. It was also found that risk for acute kidney injury were higher in population ≥ 40 years old.
Topics: Acute Kidney Injury; Adult; Antineoplastic Agents; Cisplatin; Cohort Studies; Female; Humans; Male; Mannitol; Middle Aged; Young Adult
PubMed: 35413808
DOI: 10.1186/s12885-022-09456-w -
World Journal of Gastroenterology Oct 2021The significance of plasma ascorbic acid (AA) is underscored by its enzymatic and antioxidant properties as well as involvement in many aspects of health including the... (Review)
Review
The significance of plasma ascorbic acid (AA) is underscored by its enzymatic and antioxidant properties as well as involvement in many aspects of health including the synthesis of biomolecules during acute illness, trauma and chronic health conditions. Dietary intake supports maintenance of optimal levels with supplementation at higher doses more likely pursued. Transient increased intestinal paracellular permeability following high dose AA may be utilised to enhance delivery of other micronutrients across the intestinal lumen. The potential mechanism following dietary intake however needs further study but may provide an avenue to increase small intestinal nutrient co transport and absorption, including in acute and chronic illness.
Topics: Ascorbic Acid; Humans; Intestinal Absorption; Intestinal Mucosa; Lactulose; Mannitol; Nutrients; Permeability
PubMed: 34790005
DOI: 10.3748/wjg.v27.i40.6750 -
Archives of Disease in Childhood May 1993There is a pressing need for a simple non-invasive test of exocrine pancreatic function for use in children. The pancreolauryl test has been modified by the addition of... (Comparative Study)
Comparative Study
There is a pressing need for a simple non-invasive test of exocrine pancreatic function for use in children. The pancreolauryl test has been modified by the addition of a second marker (mannitol) to achieve a single day test without the need for two timed urine collections. Six healthy subjects and nine patients with cystic fibrosis were studied. Fluorescein, fluorescein dilaurate, and mannitol were taken by mouth, alone or in combinations, followed by 10 hour urine collections in two hourly aliquots to study the comparative pharmacokinetics of these markers. Urinary fluorescein was determined spectrophotometrically and urinary mannitol enzymatically. When fluorescein dilaurate and mannitol were taken together and the results expressed as ratios of percentage fluorescein to percentage mannitol recovery (F:M ratio) (mean (SD)) there was clear discrimination between healthy subjects and those with cystic fibrosis regardless of enzyme replacement treatment (57.3 (18.2) v 3.4 (1.4) v 3.2 (1.6) respectively). The differences in F:M ratios reached statistical significance in urinary aliquots collected between two and eight hours after marker ingestion. This single day tubeless test will greatly simplify the investigation of the child with suspected exocrine pancreatic dysfunction.
Topics: Administration, Oral; Adolescent; Adult; Biomarkers; Child; Cystic Fibrosis; Female; Fluorescein; Fluoresceins; Humans; Male; Mannitol; Pancreas; Pancreatic Diseases; Pancreatic Function Tests; Time Factors
PubMed: 8323334
DOI: 10.1136/adc.68.5.649 -
AJNR. American Journal of Neuroradiology 2005This study assesses the cytotoxicity of hyperosmolar mannitol on human endothelial and meningioma cells in vitro and summarizes the initial clinical experience of using...
BACKGROUND AND PURPOSE
This study assesses the cytotoxicity of hyperosmolar mannitol on human endothelial and meningioma cells in vitro and summarizes the initial clinical experience of using mannitol as a liquid tumor embolization agent.
METHODS
Human umbilical vein endothelial cells and primary meningioma cells from surgical specimens were treated with 300, 600, 900, and 1200 mOsm of mannitol, mannitol and iohexol mixture, saline, and iohexol alone. Cell death was evaluated with a Live/Dead kit and quantified with thymidine incorporation. From 1998 to 2004, 23 patients with meningioma were treated with mannitol and 31 patients were treated with polyvinyl alcohol (PVA) particles alone. Angiographic results, procedural complications, intraoperative observation, and estimated blood loss during surgical resection were retrospectively evaluated.
RESULTS
Minimal endothelial cell death was seen after incubation with 300 mOsm of mannitol for 15 minutes, but 43 +/- 2% of endothelial cells were damaged by 1200 mOsm of mannitol after 30 minutes. Five meningioma cell lines exhibited significant cell death (22 +/- 2%; P < .05) after incubation with mannitol. Satisfactory angiographic results were obtained in all 23 patients. Tumor necrosis was observed intraoperatively and confirmed pathologically. There was no significant difference in estimated blood loss between mannitol- and PVA-embolized patients (407 +/- 64 mL vs 381 +/- 50 mL; P > .75).
CONCLUSION
High concentration of mannitol can injure endothelial cells and meningioma cells in a short period of time. It is feasible to use mannitol as a liquid embolic agent to treat meningioma.
Topics: Chemoembolization, Therapeutic; Drug Screening Assays, Antitumor; Endothelial Cells; Feasibility Studies; Humans; Mannitol; Meningioma; Osmolar Concentration; Retrospective Studies; Tumor Cells, Cultured
PubMed: 15956507
DOI: No ID Found -
The European Respiratory Journal Apr 2008Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of... (Clinical Trial)
Clinical Trial
Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of other doses is unknown. A total of 14 patients, aged 63.3+/-5.7 yrs, were studied on five visits. Mucus clearance at baseline and with mannitol (160, 320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. A control study assessed the effect of cough provoked by mannitol during the intervention. Whole right lung clearance over 45 min was 4.7+/-1.2 and 10.6+/-2.6% on baseline and control days, respectively, and increased to 16.7+/-4.2, 22.8+/-4.2 and 31+/-4.7% with 160, 320 and 480 mg mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs, was 36.1+/-5.5, 40.9+/-5.6 and 46.0+/-5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline (24.1+/-6.0%) and control (13.1+/-3.0%). Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis.
Topics: Administration, Inhalation; Aged; Bronchiectasis; Cough; Diuretics, Osmotic; Dose-Response Relationship, Drug; Female; Humans; Male; Mannitol; Middle Aged; Mucus
PubMed: 18057051
DOI: 10.1183/09031936.00119707 -
PloS One 2014Lactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal...
BACKGROUND
Lactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal lumen. Variations between currently used test protocols preclude meaningful comparisons between studies. We determined the optimal sampling period and related this to intestinal residence.
METHODS
Half-hourly lactulose and mannitol urinary excretions were determined over 6 hours in 40 healthy female volunteers after administration of either 600 mg aspirin or placebo, in randomised order at weekly intervals. Gastric and small intestinal transit times were assessed by the SmartPill in 6 subjects from the same population. Half-hourly percentage recoveries of lactulose and mannitol were grouped on a basis of compartment transit time. The rate of increase or decrease of each sugar within each group was explored by simple linear regression to assess the optimal period of sampling.
KEY RESULTS
The between subject standard errors for each half-hourly lactulose and mannitol excretion were lowest, the correlation of the quantity of each sugar excreted with time was optimal and the difference between the two sugars in this temporal relationship maximal during the period from 2½-4 h after ingestion. Half-hourly lactulose excretions were generally increased after dosage with aspirin whilst those of mannitol were unchanged as was the temporal pattern and period of lowest between subject standard error for both sugars.
CONCLUSION
The results indicate that between subject variation in the percentage excretion of the two sugars would be minimised and the differences in the temporal patterns of excretion would be maximised if the period of collection of urine used in clinical tests of small intestinal permeability were restricted to 2½-4 h post dosage. This period corresponds to a period when the column of digesta column containing the probes is passing from the small to the large intestine.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chromatography, High Pressure Liquid; Female; Gastrointestinal Transit; Healthy Volunteers; Humans; Intestine, Small; Lactulose; Mannitol; Permeability; Placebo Effect
PubMed: 24901524
DOI: 10.1371/journal.pone.0099256 -
European Journal of Pharmaceutical... Dec 2021Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with adult GH deficiency... (Clinical Trial)
Clinical Trial
Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with adult GH deficiency (AGHD) and children with GH deficiency (GHD). To date, the use of somapacitan in AGHD or severe AGHD has been approved in the USA and Japan, respectively. This study (ClinicalTrials.gov, NCT02962440) investigated the absorption, metabolism and excretion, as well as the pharmacokinetics (PK), of tritium-labelled somapacitan ([H]-somapacitan). Seven healthy males received a single subcutaneous dose of 6 mg somapacitan containing [H]-somapacitan 20 MBq. Blood, serum, plasma, urine, faeces, and expired air were collected for radioactivity assessment. Metabolites were identified and quantified in plasma and urine collected. The PK of plasma components were determined, and the radioactive peaks of the most abundant plasma metabolites and urine metabolites were selected for analysis. Twenty-eight days after dosing, 94.0% of the administered dose was recovered as [H]-somapacitan-related material, most of which was excreted in urine (80.9%); 12.9% was excreted in faeces, and an insignificant amount (0.2%) was exhaled in expired air. PK properties of [H]-somapacitan-related material appeared to be consistent across plasma, serum and blood. Three abundant plasma metabolites (P1, M1 and M1B) and two abundant urine metabolites (M4 and M5) were identified. The total exposure of intact somapacitan accounted for 59% of the total exposure of all somapacitan-related material, P1 accounted for 21% and M1 plus M1B accounted for 12%. M4 and M5 were the most abundant urine metabolites and accounted for 37% and 8% of the dosed [H]-somapacitan radioactivity, respectively. No intact somapacitan was found in excreta. Two subjects had six adverse events (AEs); all were mild in severity and unlikely to be related to trial product. The majority of dosed [H]-somapacitan (94%) was recovered as excreted metabolites. Urine was the major route for excretion of somapacitan metabolites, followed by faeces, and exhalation in expired air was negligible. The low molecular weights of identified urine metabolites demonstrate that somapacitan was extensively degraded to small residual fragments that were excreted (fully biodegradable). The extensive metabolic degradation and full elimination of metabolites in excreta were the major clearance pathways of somapacitan and the key elements in its biological fate. A single dose of 6 mg somapacitan (containing [H]-somapacitan) in healthy male subjects was well tolerated with no unexpected safety issues identified.
Topics: Administration, Cutaneous; Administration, Oral; Adult; Albumins; Child; Feces; Histidine; Human Growth Hormone; Humans; Male; Mannitol; Phenol; Research Subjects
PubMed: 34601071
DOI: 10.1016/j.ejps.2021.106030 -
Critical Care Medicine Apr 2021Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and...
OBJECTIVES
Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown.
DESIGN
A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use.
SETTING
Twenty-nine university-affiliated teaching hospitals in seven countries.
PATIENTS
A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death.
CONCLUSIONS
In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
Topics: Acute Kidney Injury; Brain Injuries, Traumatic; Diuretics, Osmotic; Erythropoietin; Female; Fluid Therapy; Humans; Intracranial Pressure; Male; Mannitol; Saline Solution, Hypertonic; Treatment Outcome
PubMed: 33566466
DOI: 10.1097/CCM.0000000000004853 -
Journal of Cystic Fibrosis : Official... May 2017Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF).
METHODS
The efficacy of inhaled mannitol in children with CF aged 6-17years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400mg every 12h or matching placebo for 8weeks, followed by an 8week washout and an 8week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1).
RESULTS
A total of 92 subjects were studied, with a mean age of 12years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p=0.004) higher compared to placebo or a 4.97% (p=0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p=0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p=0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group.
CONCLUSIONS
In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531).
Topics: Administration, Inhalation; Adolescent; Child; Cystic Fibrosis; Diuretics, Osmotic; Double-Blind Method; Drug Monitoring; Dry Powder Inhalers; Female; Forced Expiratory Volume; Humans; Male; Mannitol; Mucociliary Clearance; Quality of Life; Sputum; Treatment Outcome
PubMed: 28258928
DOI: 10.1016/j.jcf.2017.02.003 -
Pharmaceutical Research Jun 2022Gene therapy via pulmonary delivery holds the potential to treat various lung pathologies. To date, spray drying has been the most promising method to produce inhalable...
BACKGROUND
Gene therapy via pulmonary delivery holds the potential to treat various lung pathologies. To date, spray drying has been the most promising method to produce inhalable powders. The present study determined the parameters required to spray dry nanoparticles (NPs) that contain the delivery peptide, termed RALA (N-WEARLARALARALARHLARALARALRACEA-C), complexed with plasmid DNA into a dry powder form designed for inhalation.
METHODS
The spray drying process was optimised using full factorial design with 19 randomly ordered experiments based on the combination of four parameters and three centre points per block. Specifically, mannitol concentration, inlet temperature, spray rate, and spray frequency were varied to observe their effects on process yield, moisture content, a median of particle size distribution, Z-average, zeta potential, encapsulation efficiency of DNA NPs, and DNA recovery. The impact of mannitol concentration was also examined on the spray-dried NPs and evaluated via biological functionality in vitro.
RESULTS
The results demonstrated that mannitol concentration was the strongest variable impacting all responses apart from encapsulation efficiency. All measured responses demonstrated a strong dependency on the experimental variables. Furthermore, spray drying with the optimal variables in combination with a low mannitol concentration (1% and 3%, w/v) produced functional RALA/pDNA NPs.
CONCLUSION
The optimal parameters have been determined to spray dry RALA/pDNA NPs into an dry powder with excellent biological functionality, which have the potential to be used for gene therapy applications via pulmonary delivery.
Topics: Administration, Inhalation; Aerosols; DNA; Dry Powder Inhalers; Lung; Mannitol; Nanoparticles; Particle Size; Peptides; Powders
PubMed: 35441318
DOI: 10.1007/s11095-022-03256-4