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1.
Pharm Dev Technol ; 25(7): 892-898, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32321344

ABSTRACT

Praziquantel (PZQ), a broad spectrum anthelmintic drug, cannot be found in acceptable dosage forms for elderly patients, paediatric patients, and for veterinary use. In fact, very little has been done up to now in the formulation of liquid dosage forms, being they always formulated for parenteral administration. To beat this important challenge, it was accomplished a comprehensive analysis of the influence of two elementary physicochemical aspects, i.e. surface thermodynamic and electrokinetic properties, on the colloidal stability of PZQ nanosuspensions. The hydrophobic character of the drug, intensely determining the flocculation curves, was confirmed by the thermodynamic characterization. The electrophoretic characterization, in combination with the sedimentation and relative absorbance versus time curves, highlighted that the electrical double layer thickness and the surface charge can play an essential role in the stability of the pharmaceutical colloid. Finally, it was demonstrated that controlling the pH values and the incorporation of electrolytes can help in formulating PZQ aqueous nanosuspensions with appropriate stability and redispersibility behaviours for pharmaceutical use.


Subject(s)
Anthelmintics/chemical synthesis , Drug Compounding/methods , Nanospheres/chemistry , Praziquantel/chemical synthesis , Anthelmintics/pharmacokinetics , Chemistry, Pharmaceutical/methods , Electrolytes/chemical synthesis , Electrolytes/pharmacokinetics , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Nanospheres/metabolism , Praziquantel/pharmacokinetics , Water/chemistry , Water/metabolism
2.
AAPS PharmSciTech ; 20(5): 203, 2019 May 28.
Article in English | MEDLINE | ID: mdl-31139965

ABSTRACT

D-α-Tocopheryl polyethylene glycol succinate (TPGS), a polyethylene glycol condensate, is a biologically important nonionic amphiphile. In this study, we report on aqueous solution behavior of TPGS with a focus on its clouding, surface activity, micellar characteristics, and solubilization capacity for a model hydrophobic drug, carbamazepine (CBZ). Micelles were characterized by dynamic light and small-angle neutron scattering studies as a function of temperature, salt addition, and CBZ solubilization. TPGS showed a cloud point of 78°C and possessed good surface activity (as observed from surface tension reduction and adsorption parameters). The critical micelle concentration (CMC), obtained from surface tension and fluorescence studies, was 0.02 mM. Scattering studies showed formation of stable micelles (average diameter-12 nm), exhibiting no significant changes in size upon salt addition (up to 1 M NaCl), CBZ incorporation (up to 5 mM), and temperature increase (40°C). Micelles in 5 wt% TPGS showed about twentyfold enhancement in CBZ solubility. Considering the remarkable CBZ solubilization and its positioning in the core, we suggest that the formulation can be exploited as a sustained delivery vehicle.


Subject(s)
Carbamazepine/chemistry , Drug Carriers/chemistry , Micelles , Temperature , Vitamin E/chemistry , Anticonvulsants/chemistry , Anticonvulsants/pharmacokinetics , Carbamazepine/pharmacokinetics , Dose-Response Relationship, Drug , Drug Carriers/pharmacokinetics , Electrolytes/chemistry , Electrolytes/pharmacokinetics , Excipients/chemistry , Excipients/pharmacokinetics , Hydrophobic and Hydrophilic Interactions , Scattering, Small Angle , Solubility , Vitamin E/pharmacokinetics
3.
J Pharm Sci ; 108(1): 337-349, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30244009

ABSTRACT

A porous pathway feature has been added to an existing skin diffusion model to extend the range of applicability to highly polar solutes that do not readily diffuse across the stratum corneum (SC) lipid/corneocyte matrix. The porous pathway consists of 2 components: Pathway A is appendageal and is implemented as an array of aqueous shunts (the macropores), which themselves have microporous walls with transient aqueous pores (the micropores). Two varieties of shunts are discussed, one representing a terminal hair follicle and the other representing an eccrine sweat duct; however, the focus here is on the hair follicle. Pathway B is transcellular, with lipid-phase transport accomplished through defects or breaks in the bilayer lipid structure. The composite model admits polar solutes into the skin in a size-selective manner with an effective micropore radius of 1.6 nm. Steady-state permeabilities, desorption rates from isolated SC, and SC/water partition coefficients of both polar and lipophilic solutes are effectively explained.


Subject(s)
Hair Follicle/metabolism , Lipid Bilayers/metabolism , Models, Biological , Skin Absorption/physiology , Skin/metabolism , Administration, Cutaneous , Biological Transport , Biophysical Phenomena , Caffeine/pharmacokinetics , Electrolytes/pharmacokinetics , Ethanol/pharmacokinetics , Humans , Hydrophobic and Hydrophilic Interactions , In Vitro Techniques , Permeability , Porosity , Water/metabolism
4.
Adv Exp Med Biol ; 977: 59-65, 2017.
Article in English | MEDLINE | ID: mdl-28685428

ABSTRACT

Nausea and diarrhea are common yet inconsistent side effects of abdominal and pelvic irradiation. Their frequency, chronicity, and severity vary greatly, and the reasons for inter-subject variability are unknown. We studied the potential for radiation-induced changes in amino acid absorption and mucosal barrier function to lead to gastrointestinal toxicity. We found profound and prolonged changes in the absorption and secretion of several electrolytes and nutrients, caused by changes in transporter function, after radiation doses as low as 1 to 3 Gy. After identifying absorbed and non-absorbed amino acids, we demonstrated the role of a beneficial amino acid drink to alleviate radiation-related gastrointestinal symptoms in a mouse model.


Subject(s)
Amino Acids/administration & dosage , Fluid Therapy/methods , Nausea/therapy , Pica/therapy , Radiation Injuries/therapy , Rehydration Solutions/therapeutic use , Amino Acids/pharmacokinetics , Animals , Disease Models, Animal , Electrolytes/pharmacokinetics , Gastrointestinal Absorption , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/therapy , Glucose/pharmacokinetics , Male , Mice , Nausea/etiology , Pica/pathology , Radiation Injuries/complications , Rehydration Solutions/chemistry
5.
Proc Natl Acad Sci U S A ; 111(8): 2942-7, 2014 Feb 25.
Article in English | MEDLINE | ID: mdl-24516167

ABSTRACT

Nanoparticles (NPs) constitute an important medium for the targeted delivery of cancer therapeutics. Targeting of NPs to a specific cell type is traditionally achieved through the modification of the NP surface with peptides, aptamers, or other motifs that specifically recognize a cell-surface receptor, leading to internalization of NPs via clathrin and caveolae-mediated endocytosis. We have discovered that modifying the NP surface with anionic polyelectrolytes of varying lipophilicity can regulate the uptake of lipid NPs by endothelial and epithelial cells. Furthermore, we report the finding that synthetic polyelectrolytes composed of an aromatic sulfonic acid backbone exhibit specific affinity for caveolae of endothelial cells. By exploiting the higher expression of caveolae in endothelial cells in comparison with epithelial cells, a purely physiochemical approach to the targeted uptake of lipid NPs to endothelial cells is demonstrated. The ability to confer preferential affinity for NPs to cell surface domains by varying the charge and lipophilic characteristics of an NP surface offers a general means of achieving targeted delivery without the need for receptor-ligand-type targeting strategies.


Subject(s)
Caveolae/metabolism , Drug Delivery Systems/methods , Electrolytes/metabolism , Endothelial Cells/metabolism , Nanoparticles/metabolism , Neoplasms/drug therapy , Polymers/metabolism , Animals , Blotting, Western , Cell Line , Chemical Engineering/methods , Electrolytes/pharmacokinetics , Flow Cytometry , Fluorescent Antibody Technique , Humans , Mice , Microscopy, Electron, Transmission , Microscopy, Fluorescence , Nanoparticles/ultrastructure , Polymers/pharmacokinetics , Real-Time Polymerase Chain Reaction , Static Electricity , Sulfonic Acids/metabolism , Tetrazolium Salts , Thiazoles
6.
Am J Physiol Gastrointest Liver Physiol ; 301(6): G1066-74, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21903759

ABSTRACT

The intestinal transport of nutrients exhibits distinct diurnal rhythmicity, and the enterocytes harbor a circadian clock. However, temporal regulation of the genes involved in colonic ion transport, i.e., ion transporters and channels operating in absorption and secretion, remains poorly understood. To address this issue, we assessed the 24-h profiles of expression of genes encoding the sodium pump (subunits Atp1a1 and Atp1b1), channels (α-, ß-, and γ-subunits of Enac and Cftr), transporters (Dra, Ae1, Nkcc1, Kcc1, and Nhe3), and the Na(+)/H(+) exchanger (NHE) regulatory factor (Nherf1) in rat colonic mucosa. Furthermore, we investigated temporal changes in the spatial localization of the clock genes Per1, Per2, and Bmal1 and the genes encoding ion transporters and channels along the crypt axis. In rats fed ad libitum, the expression of Atp1a1, γEnac, Dra, Ae1, Nhe3, and Nherf1 showed circadian variation with maximal expression at circadian time 12, i.e., at the beginning of the subjective night. The peak γEnac expression coincided with the rise in plasma aldosterone. Restricted feeding phase advanced the expression of Dra, Ae1, Nherf, and γEnac and decreased expression of Atp1a1. The genes Atp1b1, Cftr, αEnac, ßEnac, Nkcc1, and Kcc1 did not show any diurnal variations in mRNA levels. A low-salt diet upregulated the expression of ßEnac and γEnac during the subjective night but did not affect expression of αEnac. Similarly, colonic electrogenic Na(+) transport was much higher during the subjective night than the subjective day. These findings indicate that the transporters and channels operating in NaCl absorption undergo diurnal regulation and suggest a role of an intestinal clock in the coordination of colonic NaCl absorption.


Subject(s)
Circadian Rhythm/genetics , Colon/physiology , Electrolytes/pharmacokinetics , Gene Expression Profiling , Intestinal Absorption/genetics , Aldosterone/blood , Animals , Carrier Proteins/genetics , Colon/cytology , Eating/genetics , Enterocytes/metabolism , Intestinal Mucosa/metabolism , Ion Channels/genetics , Male , Period Circadian Proteins/genetics , Rats , Rats, Wistar , Sodium Chloride, Dietary/pharmacokinetics
7.
J Trauma ; 70(5 Suppl): S17-8, 2011 May.
Article in English | MEDLINE | ID: mdl-21841561

ABSTRACT

PlasmaLyte is a family of balanced crystalloid solutions with multiple different formulations available worldwide according to regional clinical practices and preferences. It closely mimics human plasma in its content of electrolytes, osmolality, and pH. These solutions also have additional buffer capacity and contain anions such as acetate, gluconate, and even lactate that are converted to bicarbonate, CO2, and water. The advantages of PlasmaLyte include volume and electrolyte deficit correction while addressing acidosis. It shares the same problems as most other crystalloid fluids (fluid overload, edema with weight gain, lung edema, and worsening of the intracranial pressure). A unique concern is that most formulations contain magnesium, which may affect peripheral vascular resistance, heart rate, and worsen organ ischemia. There are few studies on its use in trauma or hypovolemic shock. There is no evidence that PlasmaLyte is superior to other crystalloids for the prehospital management of traumatic hypovolemia.


Subject(s)
Electrolytes/therapeutic use , Hypovolemia/therapy , Wounds and Injuries/complications , Chlorides/analysis , Electrolytes/chemistry , Electrolytes/pharmacokinetics , Emergency Medical Services/methods , Humans , Hypovolemia/blood , Hypovolemia/etiology , Infusions, Intravenous , Magnesium/analysis , Osmolar Concentration , Plasma Substitutes , Potassium/analysis , Sodium/analysis , Wounds and Injuries/blood , Wounds and Injuries/therapy
8.
Biomacromolecules ; 12(7): 2524-33, 2011 Jul 11.
Article in English | MEDLINE | ID: mdl-21604696

ABSTRACT

Nanopharmaceutics composed of a carrier and a protein have the potential to improve the activity of therapeutical proteins. Therapy for lysosomal diseases is limited by the lack of effective protein delivery systems that allow the controlled release of specific proteins to the lysosomes. Here we address this problem by developing functional polyelectrolyte-based nanoparticles able to promote acidic pH-triggered release of the loaded protein. Trimethyl chitosan (TMC) was synthesized and allowed to form polyelectrolyte complexes (PECs) with the lysosomal enzyme α-GAL through self-assembly and ionotropic gelation, with average particle size <200 nm, polydispersity index (PDI) <0.2, ζ potential of ∼ 20 mV, and a protein loading efficiency close to 65%. These polyelectrolyte nanoparticles were stable and active under physiological conditions and able to release the enzyme at acidic pH, as demonstrated by in situ atomic force microscopy (AFM). These nanoparticles were further functionalized with Atto 647N for single-particle characterization and tracking their cellular uptake and fate using high-resolution fluorescence microscopy. In contrast with their precursor, TMC, PECs were efficiently internalized by human endothelial cells and mostly accumulated in lysosomal compartments. The superior physicochemical characteristics of the TMC/α-GAL PECs together with their excellent cellular uptake properties indicate their enormous potential as advanced protein delivery systems for the treatment of lysosomal storage diseases.


Subject(s)
Chitosan/chemistry , Drug Delivery Systems , Nanocapsules/chemistry , alpha-Galactosidase/chemistry , Chitosan/chemical synthesis , Chitosan/pharmacokinetics , Electrolytes/chemical synthesis , Electrolytes/chemistry , Electrolytes/pharmacokinetics , Endothelial Cells/chemistry , Endothelial Cells/metabolism , Humans , Hydrogen-Ion Concentration , Lysosomes/chemistry , Particle Size , Surface Properties , Tissue Distribution , alpha-Galactosidase/metabolism , alpha-Galactosidase/therapeutic use
9.
Semin Dial ; 23(6): 571-4, 2010.
Article in English | MEDLINE | ID: mdl-21166878

ABSTRACT

Short daily hemodialysis (SDHD) and nocturnal home hemodialysis are modalities performed at home at shorter intervals than conventional hemodialysis. Because of their increased frequency, these alternative modalities create the potential for less inter-dialytic fluid gains and therefore fewer episodes of intra-dialytic hypotension. By more closely replicating normal renal physiology, they may also improve electrolyte management. In this article, we review published data on levels of calcium, phosphate, potassium, and bicarbonate levels using these home dialysis modalities. We also present our single-center experience with electrolyte management in patients maintained on SDHD using low dialysate flow rate, a modality of growing prevalence.


Subject(s)
Dialysis Solutions/pharmacokinetics , Electrolytes/pharmacokinetics , Hemodialysis, Home/methods , Kidney Failure, Chronic/metabolism , Water-Electrolyte Balance/drug effects , Humans , Kidney Failure, Chronic/therapy
10.
Int J Sport Nutr Exerc Metab ; 20(5): 427-42, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20975111

ABSTRACT

The purpose of this study is to summarize water, carbohydrate (CHO), and electrolyte absorption from carbohydrate-electrolyte (CHO-E) solutions based on all of the triple-lumen-perfusion studies in humans since the early 1960s. The current statistical analysis included 30 reports from which were obtained information on water absorption, CHO absorption, total solute absorption, CHO concentration, CHO type, osmolality, sodium concentration, and sodium absorption in the different gut segments during exercise and at rest. Mean differences were assessed using independent-samples t tests. Exploratory multiple-regression analyses were conducted to create prediction models for intestinal water absorption. The factors influencing water and solute absorption are carefully evaluated and extensively discussed. The authors suggest that in the human proximal small intestine, water absorption is related to both total solute and CHO absorption; osmolality exerts various impacts on water absorption in the different segments; the multiple types of CHO in the ingested CHO-E solutions play a critical role in stimulating CHO, sodium, total solute, and water absorption; CHO concentration is negatively related to water absorption; and exercise may result in greater water absorption than rest. A potential regression model for predicting water absorption is also proposed for future research and practical application. In conclusion, water absorption in the human small intestine is influenced by osmolality, solute absorption, and the anatomical structures of gut segments. Multiple types of CHO in a CHO-E solution facilitate water absorption by stimulating CHO and solute absorption and lowering osmolality in the intestinal lumen.


Subject(s)
Dietary Carbohydrates/pharmacokinetics , Electrolytes/pharmacokinetics , Exercise/physiology , Intestinal Absorption/drug effects , Intestine, Small/metabolism , Carbohydrate Metabolism/physiology , Humans , Intestinal Absorption/physiology , Osmolar Concentration , Sodium/metabolism , Water/metabolism
11.
Nutr Clin Pract ; 25(3): 250-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20581318

ABSTRACT

Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for patients with ulcerative colitis and familial polyposis coli syndromes. Pouch construction uses the distal 30-40 cm of ileum, and there exists a potential for postoperative nutrition consequences. These include vitamin B(12) deficiency, iron deficiency, bile acid malabsorption, and abnormalities of trace elements, fluids, and electrolytes. Patients who have undergone an ileal pouch-anal anastomosis procedure often describe specific food sensitivities that may require diet alteration, even more so than do patients with permanent ileostomy. There may be roles for postoperative probiotic supplementation in an attempt to decrease the rate of "pouchitis" and appropriate preoperative nutrition support to minimize the risk of perioperative complications.


Subject(s)
Colonic Pouches/adverse effects , Nutritional Sciences , Nutritional Status , Postoperative Complications , Proctocolectomy, Restorative/adverse effects , Adenomatous Polyposis Coli/surgery , Anal Canal/surgery , Anemia, Iron-Deficiency/etiology , Colitis, Ulcerative/surgery , Diet , Dietary Supplements , Electrolytes/pharmacokinetics , Humans , Ileostomy , Intestinal Absorption , Pouchitis/etiology , Pouchitis/prevention & control , Probiotics , Trace Elements/pharmacokinetics , Vitamin B 12 Deficiency/etiology
12.
Mol Imaging ; 9(1): 47-58, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20128998

ABSTRACT

One limitation of HSV1-tk reporter positron emission tomography (PET) with nucleoside analogues is the high background radioactivity in the intestine. We hypothesized that endogenous expression of thymidine kinase in bacterial flora could phosphorylate and trap such radiotracers, contributing to the high radioactivity levels in the bowel, and therefore explored different strategies to increase fecal elimination of radiotracer. Intestinal radioactivity was assessed by in vivo microPET imaging and ex vivo tissue sampling following intravenous injection of 18F-FEAU, 124I-FIAU, or 18F-FHBG in a germ-free mouse strain. We also explored the use of an osmotic laxative agent and/or a 100% enzymatically hydrolyzed liquid diet. No significant differences in intestinal radioactivity were observed between germ-free and normal mice. 18F-FHBG-derived intestinal radioactivity levels were higher than those of 18F-FEAU and 124I-FIAU; the intestine to blood ratio was more than 20-fold higher for 18F-FHBG than for 18F-FEAU and 124I-FIAU. The combination of Peptamen and Nulytely lowered intestinal radioactivity levels and increased (2.2-fold) the HSV1-tk transduced xenograft to intestine ratio for 18F-FEAU. Intestinal bacteria in germ-free mice do not contribute to the high intestinal levels of radioactivity following injection of radionucleoside analogues. The combination of Peptamen and Nulytely increased radiotracer elimination by increasing bowel motility without inducing dehydration.


Subject(s)
Herpesvirus 1, Human/enzymology , Intestines/radiation effects , Laxatives/pharmacology , Positron-Emission Tomography/methods , Radiation Protection/methods , Radiopharmaceuticals/pharmacokinetics , Thymidine Kinase/biosynthesis , Analysis of Variance , Animals , Arabinofuranosyluracil/analogs & derivatives , Arabinofuranosyluracil/pharmacokinetics , Electrolytes/pharmacokinetics , Gastrointestinal Motility/drug effects , Intestinal Mucosa/metabolism , Mice , Oligopeptides/pharmacokinetics , Polyethylene Glycols/pharmacokinetics , Rats , Thymidine Kinase/analysis , Whole Body Imaging
13.
Expert Opin Drug Deliv ; 6(6): 585-97, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19480609

ABSTRACT

The layer-by-layer (LbL) self-assembly technique has emerged as a simple and versatile method for coating biological and non-biological templates for various biomedical applications. A promising avenue of this technique lies in the encapsulation of drugs and other biological substances for controlled release. Fundamental studies of LbL assembly on flat surfaces have provided a sound understanding of film deposition theory and its pertinence to ionic and molecular transport and diffusion through polyelectrolyte multilayer (PEM) films. However, there is a lack of information on the permeability of three-dimensional PEM shell systems. In either PEM films or shells, it has been shown that drug release is a function of the ionic strength, pH and/or multilayer thickness. This report aims to provide an overview of the physicochemical parameters affecting the permeability of two- and three-dimensional multilayer shells, including ionic strength, layer number and pH. Furthermore, their synergic effect on loading and release of biologically active molecules from LbL multilayers are discussed.


Subject(s)
Delayed-Action Preparations/pharmacokinetics , Electrolytes/pharmacokinetics , Membranes, Artificial , Permeability , Adsorption , Drug Delivery Systems , Hydrogen-Ion Concentration , Kinetics , Molecular Structure , Osmolar Concentration , Static Electricity , Surface Properties
14.
J Pediatr Gastroenterol Nutr ; 48 Suppl 2: S66-71, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19300130

ABSTRACT

Colon is a crucial partner for small intestinal adaptation and function in patients who underwent extensive small intestinal resection or transplantation. This short review deals with the different properties and roles of the colon in these settings, involving fluid and electrolytes absorption, absorption of medium-chain triglycerides, and production of short-chain fatty acids for malabsorbed energy salvage. The colon may adapt after small intestinal resection, whereas it hosts the most important part of the intestinal microbiota, which plays a crucial role in intestinal function and health. Also, colon may be responsible for D-lactic acidosis as well, as it can be injured by noninfectious colitis. Finally, the relevance of a simultaneous colon grafting is discussed as it is occasionally considered in specific patients requiring intestinal transplantation.


Subject(s)
Colon/metabolism , Short Bowel Syndrome/metabolism , Acidosis, Lactic , Colon/microbiology , Colon/transplantation , Electrolytes/pharmacokinetics , Humans , Intestinal Absorption , Intestine, Small/surgery , Short Bowel Syndrome/complications , Short Bowel Syndrome/surgery , Water/physiology
15.
J Mater Sci Mater Med ; 20 Suppl 1: S229-34, 2009 Dec.
Article in English | MEDLINE | ID: mdl-18649048

ABSTRACT

In this paper we discuss the fabrication and characterization of miniaturized triglyceride biosensors on crystalline silicon and porous silicon (PS) substrates. The sensors are miniaturized Electrolyte Insulator Semiconductor Capacitors (mini-EISCAPs), which primarily sense the pH variation of the electrolyte used. The lipase enzyme, which catalyses the hydrolysis of triglycerides, was immobilized on the sensor surface. Triglyceride solutions introduced into the enzyme immobilized sensor produced butyric acid which causes the change in pH of the electrolyte. Miniaturized EISCAP sensors were fabricated using bulk micromachining technique and have silicon nitride as the pH sensitive dielectric layer. The sensors are cubical pits of dimensions 1,500 microm x 1,500 microm x 100 microm which can hold an electrolyte volume of 0.1 microl. The pH changes in the solution can be sensed through the EISCAP sensors by monitoring the flatband voltage shift in the Capacitance-Voltage (C-V) characteristics taken during the course of the reaction. The reaction rate is found to be quite high in the miniature cells when compared to the sensors of bigger dimensions.


Subject(s)
Biosensing Techniques/methods , Ion-Selective Electrodes , Miniaturization/methods , Triglycerides/analysis , Biosensing Techniques/instrumentation , Biosensing Techniques/standards , Calibration , Electrolytes/pharmacokinetics , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Lipase/chemistry , Lipase/metabolism , Models, Biological , Porosity , Semiconductors , Silicon/chemistry , Silicon/metabolism , Silicon/pharmacology
16.
Perit Dial Int ; 28 Suppl 3: S131-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18552243

ABSTRACT

In patients undergoing peritoneal dialysis (PD) for end-stage renal failure, the optimum electrolyte composition of a dialysis solution is that which best serves the homeostatic needs of the body. Comparing the transperitoneal removal of electrolytes by conventional PD solutions (CPDSs) with that by normal kidneys, it is evident that peritoneal removal is in the lower range of what can be considered "normal." Given the electrolyte composition of CPDSs and a total dwell volume of 4 exchanges of 2 L each, approximately 90 mmol NaCl, 40 mmol K(+), 10 - 15 mmol HPO(4)(-) and 1 - 2 mmol Ca(2+) can be removed daily [plus 1 L ultrafiltration (UF)]. Na(+), Ca(2+), and Mg(2+) are supplied in CPDSs in concentrations close to their plasma concentrations, which makes their removal almost entirely dependent on UF. In UF failure (UFF), plasma levels of the foregoing ions will tend to rise, producing a higher diffusion gradient to compensate for their defective UF removal. Peritoneal removal of HCO(3)(-), HPO(4)(-), and K(+) are usually quite efficient because of the zero CPDS concentrations of these ions. Approximately 150 mmol HCO(3)(-) is lost daily with CPDSs, compensated for by the addition of 30 - 40 mmol/L lactate, or, with the use of multi-compartment bags, bicarbonate instead. However, a mixture of bicarbonate and lactate should be preferred as a buffer, to avoid intracellular acidosis from high levels of pCO(2) in the dialysis fluid. For patients on continuous ambulatory peritoneal dialysis (CAPD) without UFF and with some residual renal function, PD fluid concentrations of Na(+) 130 - 133 mmol/L, Ca(2+) 1.25 - 1.35 mmol/L, and Mg(2+) 0.25 - 0.3 mmol/L seem appropriate. With reduced UF after a few years of PD, the removal of fluid and electrolytes often becomes deficient. Dietary salt restriction can be prescribed, but it is hard to implement. The use of low-Na(+) solution (LNa) is a potential alternative. The reduction in osmolality resulting from Na(+) removal in LNa should preferably be compensated by the addition of glucose (G). In a recent study, a regimen including 1 LNa exchange daily (Na(+) 115 mmol/L) in a G-compensated solution showed very promising effects on blood pressure and fluid status. However, large-scale randomized controlled studies have to be performed to definitively settle the role of LNa in volume-overloaded patients.


Subject(s)
Dialysis Solutions/chemistry , Electrolytes/analysis , Bicarbonates/metabolism , Buffers , Calcium/metabolism , Dialysis Solutions/pharmacokinetics , Electrolytes/pharmacokinetics , Humans , Lactates/metabolism , Magnesium/metabolism , Models, Biological , Peritoneal Dialysis , Peritoneum/metabolism , Sodium/metabolism , Water-Electrolyte Balance
17.
AAPS PharmSciTech ; 9(3): 924-30, 2008.
Article in English | MEDLINE | ID: mdl-18686039

ABSTRACT

The aim of this work was the development of extended release tablets of 500 mg of ciprofloxacin based on swellable drug polyelectrolyte matrices (SDPM). A set of complexes of carbomer, ciprofloxacin and sodium, (CB-Cip)(50)Na( x ), having a molar ratio Cip/CB acid groups of 0.5 and variable proportions of Na(+) was used to prepare SDPM. Characterization of complexes by FT-IR, powder X-ray diffraction and thermal analysis revealed that Cip, in its protonated form, is ionically bonded to the functional groups of CB. Rates of fluid uptake of (CB-Cip)(50)Na( x ) matrices as well as Cip release in simulated gastric fluid were modulated by changes in the proportion of Na(+) incorporated in the complexes. A direct correlation between fluid uptake and delivery rate was observed along the series of matrices. Release rates were modulated from 1.4 mg/min to 25 mg/min in going from (CB-Cip)(50)Na(10) to (CB-Cip)(50)Na(14). The analysis of kinetic data suggest that rates of swelling, ionic pair dissociation and drug diffusion play a role in the kinetic control of delivery. Complexes were satisfactorily prepared and processed together with small amounts of antiadherent and lubricant excipients to obtain a series of extended release SDPM tablets through the current tableting technology processes. Cip release from matrices was widely modulated by the composition of the complexes yielding a flexible system that allows selecting a composition that releases in 120 min 90% of the dose in simulated gastric fluid.


Subject(s)
Acrylic Resins/chemistry , Acrylic Resins/pharmacokinetics , Ciprofloxacin/chemistry , Ciprofloxacin/pharmacokinetics , Electrolytes/chemistry , Electrolytes/pharmacokinetics , Chemistry, Pharmaceutical , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Gastric Juice/chemistry , Gastric Juice/metabolism , Polymers/chemistry , Polymers/pharmacokinetics , Spectroscopy, Fourier Transform Infrared , Tablets
18.
BMC Surg ; 8: 10, 2008 Jun 09.
Article in English | MEDLINE | ID: mdl-18541019

ABSTRACT

BACKGROUND: Postoperative deaths and neurological injury have resulted from hyponatraemia associated with the use of hypotonic saline solutions following surgery. We aimed to determine the rates and types of intravenous fluids being prescribed postoperatively for children in the UK. METHODS: A questionnaire was sent to members of the British Association of Paediatric Surgeons (BAPS) and Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) based at UK paediatric centres. Respondents were asked to prescribe postoperative fluids for scenarios involving children of different ages. The study period was between May 2006 and November 2006. RESULTS: The most frequently used solution was sodium chloride 0.45% with glucose 5% although one quarter of respondents still used sodium chloride 0.18% with glucose 4%. Isotonic fluids were used by 41% of anaesthetists and 9.8% of surgeons for the older child, but fewer for infants. Standard maintenance rates or greater were prescribed by over 80% of respondents. CONCLUSION: Most doctors said they would prescribe hypotonic fluids at volumes equal to or greater than traditional maintenance rates at the time of the survey. A survey to describe practice since publication of National Patient Safety Agency (NPSA) recommendations is required.


Subject(s)
Fluid Therapy/classification , Fluid Therapy/statistics & numerical data , Hypotonic Solutions/administration & dosage , Postoperative Care/classification , Postoperative Care/statistics & numerical data , Appendectomy , Child , Cysts/surgery , Drug Administration Schedule , Drug Dosage Calculations , Electrolytes/administration & dosage , Electrolytes/pharmacokinetics , Gastrointestinal Diseases/surgery , Glucose/administration & dosage , Health Care Surveys , Humans , Hypoglycemia/therapy , Hyponatremia/chemically induced , Hypotonic Solutions/adverse effects , Hypotonic Solutions/classification , Infant , Infant, Newborn , Infusions, Intravenous , Intussusception/surgery , Isotonic Solutions/administration & dosage , Laparotomy , Medication Errors/statistics & numerical data , Monitoring, Physiologic , Prescriptions/statistics & numerical data , Surveys and Questionnaires , United Kingdom/epidemiology
19.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 20(3): 163-6, 2008 Mar.
Article in Chinese | MEDLINE | ID: mdl-18328130

ABSTRACT

OBJECTIVE: To investigate the intestinal absorption rate of glucose-electrolyte solution (GES) during enteral resuscitation of burn injury in Beagle dogs, and compare the effect of enteral intake with that of intravenous infusion resuscitation. METHODS: Twelve male Beagle dogs were subjected to a 35% total body surface area (TBSA) full-thickness flame III degree injury. Thirty minutes after burn, each dog was given either enteral resuscitation with a GES (EGES group) or intravenous resuscitation with lactated Ringer's solution (IVLR group), and the amount and speed of replenishment of fluid were in accordance with Parkland formula. In the first 8 hours post burn, intestinal absorption rates of water and Na+ were continuously assessed using phenol red as a nonabsorbable marker for water absorption rate. The plasma volume (PV) was measured by the dye (indocyanine green) dilution technique, and the plasma concentration of Na+, mean arterial pressure (MAP) cardiac output (CO), and urine volume were also determined in the first 8 hours. All above measurement were performed in animals without anesthesia. At the end of 8-hour-period of experiment, the remnant fluids in the intestine were collected to calculate the total volume of fluid absorbed in 8 hours. RESULTS: The intestinal absorption rates of water and Na+ reduced markedly down to lowest level (21% and 37% of pre-injury level) at 3.5 hours post burn, and then increased slowly. But the mean absorption rate of water was similar to infusing rate according to Parkland formula [(99+/-47) mlxh(-1)xm(-1) vs. (81+/-11) mlxh(-1)xm(-1), P>0.05]. The total fluid absorbed by intestine was (94.8+/-3.7)% of the total fluid infused within 8 hours post burn. There were no significant differences in plasma concentration of Na+, MAP and CO between two groups at 8 hours post burn. The urine volume and PV at 4 hours in EGES group were lower than those in IVLR group (both P<0.05), but those indexes at 8 hours showed no significant difference between two groups (both P>0.05). CONCLUSION: Intestinal absorption rate of fluid given according to Parkland formula after burn injury is sufficient to resuscitate shock in animals suffering from a 35%TBSA full-thickness burn. Enteral resuscitation with GES may attain a similar therapeutic effect in expanding PV and maintain hemodynamic parameters.


Subject(s)
Burns/therapy , Electrolytes/pharmacokinetics , Glucose/pharmacokinetics , Intestinal Absorption/physiology , Resuscitation/methods , Animals , Body Surface Area , Disease Models, Animal , Dogs , Electrolytes/therapeutic use , Fluid Therapy/methods , Glucose/therapeutic use , Infusions, Intravenous , Intestine, Small/metabolism , Isotonic Solutions/therapeutic use , Male , Ringer's Lactate
20.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 20(3): 167-71, 2008 Mar.
Article in Chinese | MEDLINE | ID: mdl-18328131

ABSTRACT

OBJECTIVE: To investigate the effect of carbachol (CAR) on blood flow of intestinal mucosa and absorption rate of glucose-electrolyte solution (GES) during enteral resuscitation of burn shock in dog. METHODS: Eighteen male Beagle dogs were subjected to a (51.2+/-2.6)% total body surface area (TBSA) full-thickness flame injury, and fluid resuscitation was given according to Parkland formula 0.5 hour after burn. Animals were randomly divided into intravenous infusion of GES group (VGES group, n=6), enteral infusion of GES group (EGES group, n=6) and EGES containing 0.25 microg/kg of CAR group (EGES/CAR group n=6). In the first 8 hours post burn, intestinal absorption rate of water and Na+, intestinal mucosa blood flow (IBF), the plasma volume (PV) and plasma concentration of Na+ were continuously determined without anesthesia. At the end of 8 hours animals were sacrificed, and specimens of gut tissue were taken to determine the activity of Na+-K+-ATPase. RESULTS: The intestinal absorption rate of water and Na+ was reduced markedly after burn in two enteral resuscitation groups and much lower than pre-injury levels and the expected infusing rate according to Parkland formula. It was found that the absorption rate of water and Na+ from 1.5 hours and 2.5 hours in EGES/CAR group were significantly higher compared with those in EGES group (all P<0.05). During 8 hours after burn, only 47.1% and 63.8% of fluids enterally infused in EGES and EGES/CAR groups were absorbed by the gut. The volume of fluid absorbed and the fluid absorption rate were significantly higher in EGES/CAR group than those in EGES group (P<0.05). Incidence of gut intolerance (diarrhea) was 83% in EGES group, which was higher than that of in EGES/CAR group (50%). IBF was significantly decreased compared with pre-injury levels in all groups. Enteral infusion of CAR led to a significant elevation of IBF in EGES/CAR compared with GES group from 4 hours after burn, but it was still lower than pre-injury levels and those in VGES group. The Na+-K+-ATPase activity between three groups ranked as follows: VGES group>EGES/CAR group>EGES group (P<0.05). Within 8 hours post injury, PV and plasma concentration of Na+ in two enteral resuscitation groups were much lower than those in VGES group, but from 4 hours after burn the values in EGES/CAR group were higher than those in EGES group (all P<0.05). CONCLUSION: 50%TBSA full-thickness flame injury led to a markedly decrease in intestinal absorption rate of water and Na+. The total volume of fluid absorbed by intestine in 8 hours was significantly lower in enteral resuscitation groups compared to the regime of the Parkland formula. CAR promoted intestinal absorption rate and PV by increasing the intestinal blood flow and Na+-K+-ATPase activity, and it seems to exert a helpful effect on the resuscitation of burn shock with electrolyte solution per oral route.


Subject(s)
Burns/physiopathology , Carbachol/pharmacology , Fluid Therapy , Intestinal Absorption/drug effects , Regional Blood Flow/drug effects , Animals , Burns/therapy , Disease Models, Animal , Dogs , Electrolytes/pharmacokinetics , Electrolytes/therapeutic use , Glucose/pharmacokinetics , Glucose/therapeutic use , Intestinal Mucosa/blood supply , Male , Resuscitation
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