Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage

Context

Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose.

Case Details

A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient’s recovery revealed exposure to snorted fentanyl powder immediately prior to presentation.

Discussion

Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication.

Conclusions

Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

     

Glucose-Based Mesoporous Carbon Nanospheres as Functional Carriers for Oral Delivery of Amphiphobic Raloxifene: Insights into the Bioavailability Enhancement and Lymphatic Transport

Purpose

Oral therapy with raloxifene (RXF), an amphiphobic drug for remedy of the postmenopausal osteoporosis and estrogen-dependent breast cancer, is less effective due to its poor bioavailability (2% or so). This work aimed to devise mesoporous carbon nanospheres (MCNs) for oral delivery of RXF and evaluate their performance in bioavailability enhancement and lymphatic transport.

Methods

Glucose-based MCNs were fabricated by hydrothermal reaction followed by high-temperature activation. RXF-loaded MCNs (RXF-MCNs) were prepared by solvent-diffusion/high-pressure homogenization and stabilized by phospholipid. RXF-MCNs were fully characterized by particle size, morphology, in vitro drug release and metabolism, in vivo pharmacokinetics and lymphatic transport, and ex vivo fluorescent imaging.

Results

The prepared RXF-MCNs were 230 nm around in particle size, showing high entrapment efficiency (95.35%) and satisfactory physical stability. The oral bioavailability of RXF was enhanced by 2.07 folds through MCNs compared with RXF suspensions in rats. It was shown that reduced intestinal metabolism due to entrapment into MCNs, active transcellular uptake and increased lymphatic transport were responsible for enhanced bioavailability as a result of transport improvement.

Conclusions

The results suggest that MCNs are suitable nanocarriers for oral delivery of poorly bioavailable RXF.

     

Application of Lipid Blend-Based Nanoparticulate Scaffold for Oral Delivery of Antihypertensive Drug: Implication on Process Variables and In Vivo Absorption Assessment

Purpose

The aim of the present study was to formulate and optimize lipid blend-based olmesartan medoxomil (OLM) loaded nanoparticulate scaffolds (NLCs) for enhanced oral bioavailability.

Method

The OLM-NLCs were formulated using dependent variables in different concentrations of solid lipid, liquid lipid, surfactant, and co-surfactant by using melt emulsification combined with ultrasonication technique. The formulations were experimentally optimized using a three-factor, three-level statistical design approach. The formulated OLM-NLCs were evaluated for various pharmaceutical quality evaluation parameters and further optimized formulation (OLM-NLCopt) was assessed for release kinetics, thermal behavior, and in vivo absorption assessment.

Result

The optimized formulation (OLM-NLCopt) showed particle size (138.7 nm), PDI (0.18), and entrapment efficiency (83.65%). The comparative in vitro release study revealed OLM-NLCopt showed significantly higher (p?<?0.05) drug release compare to OLM-susp. The in vivo study showed the OLM-NLCopt indicated nearly 3-fold improvement in oral bioavailability vis-a-vis OLM-susp in mice model.

Conclusion

The results of the release study and pharmacokinetic study suggest the potential of OLM-NLCs for improved oral delivery.

     

Improved Stability and Enhanced Oral Bioavailability of Atorvastatin Loaded Stearic Acid Modified Gelatin Nanoparticles

Purpose

The present study evaluates the effects of stearic acid conjugation with gelatin and, its pharmaceutical potential to formulate novel atorvastatin (AT) loaded nanoparticles.

Method

AT loaded stearic acid modified gelatin nanoparticles (AT-MG NPs) were prepared via two-step desolvation method with extensive optimization of different process variables. Further, the developed nanoparticles where evaluated against in vitro Caco-2 cell model and in vivo bioavailability.

Results

Extensive optimization of nanoformulation resulted into the formation of AT-MG NPs with particle size 247.7 ± 10.9 nm, PDI 0.219 ± 0.07, and entrapment efficiency 58.7 ± 5.3%. Freeze dried nanoparticles were found to have spherical shape as determined by SEM and demonstrated excellent stability in simulated gastrointestinal conditions and during storage. Developed nanoparticles exhibited sustained release up to 24 h and remarkably higher Caco-2 cell uptake. Mechanistic studies further revealed the clathrin and caveolae mediated endocytosis as principle mechanism. In line with Caco-2 cell uptake observations, AT-MG NPs showed ～4.84-fold increase in the AUC0-∞ values of AT in comparison with free AT following oral administration.

Conclusion

Overall, the stearic acid conjugated gelatin NPs demonstrates a promising potential in improving the drug payload of BCS class II drugs and enhancing oral bioavailability.

     

The effects of buprenorphine on fentanyl withdrawal in rats

Rationale

Fentanyl is a potent mu-opioid receptor agonist that is widely used for the treatment of severe chronic pain. Discontinuation of fentanyl administration has been shown to induce a negative emotional state.

Objectives

The aim of the present studies was to investigate the effects of the partial mu-opioid receptor agonist buprenorphine on the negative emotional state associated with precipitated and spontaneous fentanyl withdrawal in rats.

Materials and methods

Fentanyl and saline were chronically administered via osmotic minipumps. A discrete-trial intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs.

Results

Naloxone induced a deficit in brain reward function in rats chronically treated with fentanyl. Buprenorphine dose-dependently prevented the naloxone-induced deficit in brain reward function. Discontinuation of fentanyl administration was also associated with a deficit in brain reward function. After explantation of the minipumps, the administration of buprenorphine induced a potentiation of brain reward function in the fentanyl-withdrawing rats, but did not affect brain reward function of saline-treated control rats. Buprenorphine prevented the somatic withdrawal signs associated with spontaneous fentanyl withdrawal and attenuated the somatic signs associated with precipitated fentanyl withdrawal.

Conclusions

Buprenorphine prevents affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is rewarding in rats previously exposed to fentanyl, but not in opioid-naïve rats. This pattern of results suggests that buprenorphine may be an effective treatment for the anhedonic-state associated with fentanyl withdrawal, but further study of buprenorphine’s abuse potential is warranted.

     

<Emphasis Type="BoldItalic">In Silico</Emphasis> Absorption Analysis of Valacyclovir in Wildtype and <Emphasis Type="BoldItalic">Pept1</Emphasis> Knockout Mice Following Oral Dose Escalation

Purpose

We developed simulation and modeling methods to predict the in vivo pharmacokinetic profiles of acyclovir, following escalating oral doses of valacyclovir, in wildtype and Pept1 knockout mice. We also quantitated the contribution of specific intestinal segments in the absorption of valacyclovir in these mice.

Methods

Simulations were conducted using a mechanistic advanced compartmental absorption and transit (ACAT) model implemented in GastroPlus?. Simulations were performed for 3 h post-dose in wildtype and Pept1 knockout mice following single oral doses of 10, 25, 50 and 100 nmol/g valacyclovir, and compared to experimentally observed plasma concentration-time profiles of acyclovir.

Results

Good fits were obtained in wildtype and Pept1 knockout mice. Valacyclovir was primarily absorbed from duodenum (42%) and jejunum (24%) of wildtype mice, with reduced uptake from ileum (3%) and caecum/colon (1%), for a total of 70% absorption. In contrast, the absorption of valacyclovir in Pept1 knockout mice was slow and sustained throughout the entire intestinal tract in which duodenum (4%), jejunum (14%), ileum (10%) and caecum/colon (12%) accounted for a total of 40% absorption.

Conclusion

The ACAT model bridged the gap between in situ and in vivo experimental findings, and facilitated our understanding of the complicated intestinal absorption processes of valacyclovir.

     

Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone®

Purpose

Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it.

Materials and Methods

The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats.

Results

The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6?±?2.9 nm with 34.5?±?2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone®. The relative oral bioavailability of the AMB-NP was found to be ～800% as compared to Fungizone®.

Conclusion

Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities.

     

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology

Purpose

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles.

Methods

NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references.

Results

NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C _max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation.

Conclusion

Controlled release of integral NLCs is achieved by the osmotic pump strategy.

     

<Emphasis Type="BoldItalic">In Vitro</Emphasis> and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Characterization of Drug Nanoparticles Prepared Using PureNano™ Continuous Crystallizer to Improve the Bioavailability of Poorly Water Soluble Drugs

Purpose

The aim of this study was to enhance the dissolution and oral absorption of poorly water-soluble active pharmaceutical ingredients (APIs) using nanoparticle suspensions prepared with a PureNano? continuous crystallizer (PCC).

Method

Nanoparticle suspensions were prepared with a PCC, which is based on microfluidics reaction technology and solvent–antisolvent crystallization. Phenytoin, bezafibrate, flurbiprofen, and miconazole were used as model APIs. These APIs were dissolved in ethanol and precipitated by the addition of water and polyvinyl alcohol. Batch crystallization (BC) using a beaker was also performed to prepare the suspensions. Both PCC and BC formulations were freeze-dried before being characterized in vitro and in vivo.

Results

The particle sizes of the nanoparticle suspensions prepared with the PCC were smaller than those prepared by BC. The dissolution rate of each API in vitro significantly increased after crystallization. Reducing the particle size of either the BC or PCC formulation led to increased API flux across Caco-2 cell monolayers. PCC preparations showed higher plasma concentrations after oral administration, demonstrating the advantages of a fast dissolution rate and increased interaction with the gastrointestinal tract owing to the smaller particle size.

Conclusions

PCC can continuously produce nanoparticle APIs and is an efficient approach for improving their oral bioavailability.

     

Blood Urea Nitrogen/Creatinine Ratio and Response to Tolvaptan in Patients with Decompensated Heart Failure: A Retrospective Analysis

Introduction

Arginine vasopressin-stimulated reabsorption of urea occurs in the collecting duct via increased expression of the urea transporter.

Objective

The aim of this study was to evaluate whether the blood urea nitrogen/creatinine (BUN/Cr) ratio is useful for predicting tolvaptan response in patients with decompensated heart failure (HF).

Methods

Among 71 consecutive patients with HF who received oral tolvaptan between 2010 and 2014, we retrospectively studied 33 patients with decompensated HF without any mechanical circulatory assistance or inotropic support who had already been treated with loop diuretics. A responder to tolvaptan was defined as an individual who experienced a ≥30 % increase in their respective 24-h urine volume.

Results

Among the 33 patients, 21 met the criteria of a responder. The area under the receiver operating characteristic curves of BUN/Cr and BUN were 0.790 and 0.714, respectively, and the respective cut-off values for responders to tolvaptan were 23.8 and 49.0. BUN/Cr and BUN retained their significant relationships with the responder status (odds ratio for BUN/Cr >23.8: 20.9; 95 % confidence interval [CI] 2.7–531.1; p = 0.002; odds ratio for BUN ≥49: 7.7; 95 % CI 1.4–65.8; p = 0.02).

Conclusion

Our results suggest that high BUN/Cr may be a predictor of response to tolvaptan in decompensated HF patients. A prospective study with a large sample size is required to confirm this preliminary finding.

     

Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis

Purpose

Analog development of existing drugs and direct drug delivery to the lungs by inhalation as treatments for multiple and extensively drug resistant (MDR and XDR) tuberculosis (TB) represent new therapeutic strategies. Pyrazinamide (PZA) is critical to drug sensitive TB therapy and is included in regimens for MDR TB. However, PZA-resistant Mycobacterium tuberculosis (Mtb) strains threaten its use. Pyrazinoic acid esters (PAEs) are PZA analogs effective against Mtb in vitro, including against the most common PZA resistant strains. However, PAEs require testing for TB efficacy in animal models.

Methods

PAEs were delivered daily as aqueous dispersions from a vibrating mesh nebulizer to Mtb infected guinea pigs for 4 weeks in a regimen including orally administered first-line TB drugs.

Results

PAEs tested as a supplement to oral therapy significantly reduced the organ bacterial burden in comparison to infected, untreated control animals. Thus, PAE aerosol therapy is a potentially significant addition to the regimen for PZA resistant MDR-TB and XDR-TB treatment. Interestingly, low dose oral PZA treatment combined with standard therapy also reduced bacterial burden. This observation may be important for PZA susceptible disease treatment.

Conclusion

The present study justifies further evaluation of PZA analogs and their lung delivery to treat TB.

     

A Retrospective Study of Clinical Effects of Powdered Caffeine Exposures Reported to Three US Poison Control Centers

Introduction

Anhydrous caffeine, often sold on the Internet as a powdered caffeine product, is sold as “pure caffeine” to be used as an additive to beverages and has also been used as an ingredient in energy supplement products.

Methods

This is a retrospective multiple-poison center chart review of calls regarding powdered caffeine to poison centers covering Oregon, Alaska, Guam, Washington, and Utah between January 1, 2013 and June 30, 2015.

Results

There were 40 calls to three poison centers over 30 months for powdered caffeine exposure. The majority of patients were over age 19 (52.5 %; 21/40) and male (70 %; 28/40). Sixty percent (24/40) of the patients were symptomatic but only 10 % (4/40) required admission; 52.5 % (21/40) of the patient calls were for inadvertent overdose of powdered caffeine; one patient overdosed in a self-harm attempt.

Discussion

Powdered caffeine calls to three poison centers during a 30-month study period were rare, and severe caffeine toxicity due to exposure was found in few patients. The majority of symptoms were reported after an inadvertent powdered caffeine overdose.

Conclusions

An analysis of calls to three poison centers for powdered caffeine found that exposures were uncommon, but did result in toxicity, and highlighted that the lack of clear dosing instructions on product packaging may place patients at risk of inadvertent overdose.

     

Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model

Purpose

Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin’s effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia.

Methods

A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous).

Results

The plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K _m ?=?44.1 mg/kg, V _max ?=?41.9 mg/h?kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E _max function describing reversal of hyperalgesia (EC _{50, plasma} ?=?16.7 μg/mL, EC _{50, brain} ?=?3.3 μg/mL).

Conclusions

The proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin’s non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.

     

A Study on Toxicity of Chemically Synthesised Silver Nanoparticle on <Emphasis Type="Italic">Eudrilus eugeniae</Emphasis>

Objective

To evaluate the toxicity of the silver nanoparticle against earthworms - Eudrilus eugeniae, a model for soil organism.

Methods

Silver nanoparticles were synthesised by chemical reduction and further characterised by UV Visible Spectroscopy and FeSEM. Earthworms were allowed to interact with different concentrations of the synthesized silver nanoparticles. After exposure period, histology and inductively coupled plasma optical emission spectrometry (ICP-OES) were done to determine the accumulation and toxic effects exhibited by the nanoparticle on earthworms.

Results

The synthesized nanoparticle was found to be between the size of 180 and 200 nm. Histology studies revealed that silver nanoparticles to cause fibrosis, lipofuscin-like deposits and also gut disruption in earthworms.

Conclusion

Silver nanoparticles were found to be toxic to Eudrilus eugeniae, which was evidenced by histology.

     

Preparation and Evaluation of a Novel Class of Amphiphilic Amines as Antitumor Agents and Nanocarriers for Bioactive Molecules

Purpose

We describe a novel class of antitumor amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length.

Methods

We tested the lead compound, RC16, for cytotoxicity and mechanism of cell death in several cancer cell lines, anti tumor efficacy in mouse tumor models, and ability to encapsulate chemotherapy drugs.

Results

These compounds displayed strong cytotoxic activity against cell lines derived from both pediatric and adult cancers. The IC50 of the lead compound, RC16, for normal cells including human keratinocytes, human fibroblasts and human umbilical vein endothelial cells was tenfold higher than for tumor cells. RC16 exhibited significant antitumor effects in vivo using several human xenografts and a metastatic model of murine neuroblastoma by both intravenous and oral administration routes. The amphiphilic character of RC16 triggered a spontaneous molecular self-assembling in water with formation of micelles allowing complexation of Doxorubicin, Etoposide and Paclitaxel. These micelles significantly improved the in vitro antitumor activity of these drugs as the enhancement of their aqueous solubility also improved their biologic availability.

Conclusions

RC16 and related amphiphilic amines may be useful as a novel cancer treatment.

     

Dinitrophenol (DNP) Fatality Associated with a Falsely Elevated Salicylate Level: a Case Report with Verification of Laboratory Cross Reactivity

Introduction

2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically leads to hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Intentional overdoses of DNP are often fatal. We present an analytically confirmed fatal case of DNP overdose with a falsely positive elevated salicylate concentration. We further explored this cross reactivity of DNP with two salicylate assays.

Methods

Clinically relevant serial dilutions of DNP were prepared in drug-free serum and analyzed using two different colorimetric NADH/NAD-based analytical methodologies.

Results

The enzymatic salicylate assay demonstrated a reproducible false elevation of salicylate starting at a DNP level of 100 mg/L while the EMIT-based methodology was without any such interference at the maximum concentration tested (150 mg/L).

Conclusions

DNP cross reacts with some salicylate assays. This knowledge is important for providers, as there are significant variations in the management of DNP versus salicylate toxicity.

     

Lyophilized Nanosuspensions for Oral Bioavailability Improvement of Insoluble Drugs: Preparation,Characterization, and Pharmacokinetic Studies

Purpose

We describe here a novel lyophilized nanosuspension technology in order to improve the dissolution rate and oral bioavailability of the insoluble drug P2X7 receptor antagonist (PRA), which is an effective antagonist to P2X7 receptor for non-steroidal anti-inflammatory.

Methods

PRA-lyophilized nanosuspension (PRA-LNS) was fabricated by anti-solvent precipitation in combination with high pressure homogenization, and then lyophilized for prolonged storage. After preparations, various characterization experiments were performed including particle size, zeta potential, surface morphology, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), in vitro dissolution study, and in vivo pharmacokinetic study.

Results

The re-dissolved particle size of PRA-LNS was about 180~250 nm with uniform distribution, confirmed by TEM image. The drug PRA in nanosuspensions possessed crystalline form evaluated via XRPD and DSC analysis. The solubility of PRA-LNS in water was 1.52 times larger than PRA raw drug; in vitro dissolution tests showed that PRA-LNS could dissolve completely within 5 min, which is a significant improvement compared to the raw drug. The relative bioavailability of PRA-LNS is 290.70% compared to the raw drug and 177.94% compared to the physical mixture.

Conclusions

PRA-LNS could easily re-disperse in water with increased solubility, enhanced oral bioavailability, and controllable production process.

     

Physicochemical Properties of Solid Phospholipid Particles as a Drug Delivery Platform for Improving Oral Absorption of Poorly Soluble Drugs

Purpose

A novel drug delivery platform, mesoporous phospholipid particle (MPP), is introduced. Its physicochemical properties and ability as a carrier for enhancing oral absorption of poorly soluble drugs are discussed.

Methods

MPP was prepared through freeze-drying a cyclohexane/t-butyl alcohol solution of phosphatidylcholine. Its basic properties were revealed using scanning electron microscopy, x-ray diffraction, thermal analysis, hygroscopicity measurement, and so on. Fenofibrate was loaded to MPP as a poorly soluble model drug, and effect of MPP on the oral absorption behavior was observed.

Results

MPP is spherical in shape with a diameter typically in the range of 10–15 μm and a wide surface area that exceeds 10 m²/g. It has a bilayer structure that may accommodate hydrophobic drugs in the acyl chain region. When fenofibrate was loaded in MPP as a model drug, it existed partially in a crystalline state and improvement in the dissolution behavior was achieved in the presence of a surfactant, because of the formation of mixed micelles composed of phospholipids and surfactants in the dissolution media. MPP greatly improved the oral absorption of fenofibrate compared to that of the crystalline drug and its efficacy was almost equivalent to that of an amorphous drug dispersion.

Conclusion

MPP is a promising option for improving the oral absorption of poorly soluble drugs based on the novel mechanism of dissolution improvement.

     

Laxative Effects of Triple-Fermented Barley Extracts (Fbe) in Normal Rats

Objective

The purpose of this study was to observe the possible laxative effects of a triple-fermented barley (Hordeum vulgare L.) extract (FBe) obtained by saccharification and by using Saccharomyces cerevisiae and Weissella cibaria in normal rats.

Methods

Forty rats (8 rats in five groups) were selected and used after 10 d of acclimatization. FBe at concentrations of 100, 200, or 300 mg/kg was orally administered once a day for 15 d, and the changes in fecal parameters, gastrointestinal transit ratio, fecal mucus content, and colonic mucosa histology, were observed in normal rats. The laxative effects of FBe were compared against those of sodium picosulfate.

Results

By assessing the key parameters for laxative effects in rats, the present study demonstrated that oral administration of 200 and 300 mg/kg FBe showed favorable laxative effects, mediated by increases in gastrointestinal motility. However, restricted effects were observed when using 100 mg/kg FBe, at least under the experimental conditions presented here.

Conclusion

Based on these results, we conclude that FBe is promising as a new potent laxative agent or as an ingredient in functional foods, with low toxicity at a dose level of 200 mg/kg in normal rats.