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Bioavailability
Kinds of Bioavailability Terms modified by Bioavailability Selected AbstractsEffects of oyster extract on the reproductive function of zinc-deficient mice: Bioavailability of zinc contained in oyster extractCONGENITAL ANOMALIES, Issue 4 2003Yoshikazu Matsuda ABSTRACT Zinc is a vital nutrient in the normal reproductive function and embryonic development of mammals, and it is well known that oyster extract contains significant amounts of zinc. The effects of oyster extract on reproductive function, such as embryonic development, serum levels of zinc and sperm maturation were examined in zinc-deficient mice. Zinc deficiency in dams during pregnancy induced a decrease in the successful pregnancy rate, maternal weight gain, the number of live fetuses and fetal body weight. Zinc deficiency for 12 weeks in male mice induced a decrease in body weight, testis weight and sperm count in the epididymis. However, reproductive failure, embryonic defects and decreased sperm motility in zinc-deficient mice were improved by supplementation with oyster extract. Some nutrients contained in oyster extract, such as taurine and glycogen, may be related to the recovery of reproductive function. There were significantly lower serum concentrations of zinc in dams fed a zinc-deficient diet However, the serum zinc concentration was normal in the oyster extract-supplemented group. No difference in the concentration of serum zinc was observed between the oyster extract- and zinc carbonate-supplemented groups. From these findings, it is suggested that oyster extract is a useful supplement that can prevent reproductive defects from zinc deficiency, and the bioavailability of zinc may be identical to zinc carbonate. [source] Trace Metals in Anaerobic Granular Sludge Reactors: Bioavailability and Dosing StrategiesENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 3 2006H. Zandvoort Abstract The trace metal dynamics in anaerobic granular sludge bed reactors and their influence on reactor performance is reviewed in this paper. An insight into the metal dynamics is required from a practical point of view in order to be able to early recognize limitations for essential trace elements, viz., to know when dosing of these elements is required in full-scale anaerobic bioreactor applications. Further such knowledge is indispensable for a rational dosage of these metals, e.g., to ensure maximum substrate conversion rates and to prevent disturbances in reactor performance using a minimum amount of metals. Therefore, the retention, accumulation and release of trace metals in anaerobic granular sludge and the factors affecting these processes need to be known. [source] Bioavailability of solid and non-aqueous phase liquid (NAPL)-dissolved phenanthrene to the biosurfactant-producing bacterium Pseudomonas aeruginosa 19SJENVIRONMENTAL MICROBIOLOGY, Issue 9 2001Marta García-Junco The biodegradation of phenanthrene by the biosurfactant-producing strain Pseudomonas aeruginosa 19SJ was investigated in experiments with the compound present either as crystals or dissolved in non-aqueous phase liquids (NAPLs). Growth on solid phenanthrene exhibited an initial phase not limited by dissolution rate and a subsequent, carbon-limited phase caused by exhaustion of the carbon source. Rhamnolipid biosurfactants were produced from solid phenanthrene and appeared in solution and particulate material (cells and phenanthrene crystals). During the carbon-limited phase, the concentration of rhamnolipids detected in culture exceeded the critical micelle concentration (CMC) determined with purified rhamnolipids. The biosurfactants caused a significant increase in dissolution rate and pseudosolubility of phenanthrene, but only at concentrations above the CMC. Externally added rhamnolipids at a concentration higher than the CMC increased the biodegradation rate of solid phenanthrene. Mineralization curves of low concentrations of phenanthrene initially dissolved in two NAPLs [2,2,4,4,6,8,8-heptamethylnonane and di(2-ethylhexyl)phthalate] were S-shaped, although no growth was observed in the population of suspended bacteria. Biosurfactants were not detected in solution under these conditions. The observed mineralization was attributed not only to suspended bacteria, but also to bacterial populations growing at the NAPL,water interface, mineralizing the compound at higher rates than predicted by abiotic partitioning. We suggest that rhamnolipid production and attachment increased the bioavailability of phenanthrene, so promoting biodegradation activity. [source] Bioavailability of decabromodiphenyl ether to the marine polychaete Nereis virensENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2010Susan L. Klosterhaus Abstract The flame retardant decabromodiphenyl ether (BDE 209) accumulates in humans and terrestrial food webs, but few studies have reported the accumulation of BDE 209 in aquatic biota. To investigate the mechanisms controlling the bioavailability of BDE 209, a 28-d bioaccumulation experiment was conducted in which the marine polychaete worm Nereis virens was exposed to a decabromodiphenyl ether (deca-BDE) commercial mixture (>85% BDE 209) in spiked sediments, in spiked food, or in field sediments. Bioaccumulation from spiked substrate with maximum bioavailability demonstrated that BDE 209 accumulates in this species. Bioavailability depends on the exposure conditions, however, because BDE 209 in field sediments did not accumulate (<0.3 ng/g wet weight; 28-d biota-sediment accumulation factors [BSAFs] <0.001). When exposed to deca-BDE in spiked sediments also containing lower brominated congeners (a penta-BDE mixture), bioaccumulation of BDE 209 was 30 times lower than when exposed to deca-BDE alone. Selective accumulation of the lower brominated congeners supports their prevalence in higher trophic level species. The mechanisms responsible for limited accumulation of BDE 209 may involve characteristics of the sediment matrix and low transfer efficiency in the digestive fluid. Environ. Toxicol. Chem. 2010;29:860,868. © 2009 SETAC [source] Bioavailability and biodegradation of nonylphenol in sediment determined with chemical and bioanalysis,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2008Jasperien de Weert Abstract The surfactant nonylphenol (NP) is an endocrine-disrupting compound that is widely spread throughout the environment. Although environmental risk assessments are based on total NP concentrations, only the bioavailable fraction posses an environmental risk. The present study describes the bioavailability and biodegradability of NP over time in contaminated river sediment of a tributary of the Ebro River in Spain. The bioavailable fraction was collected with Tenax TA® beads, and biodegradation was determined in aerobic batch experiments. The presence of NP was analyzed chemically using gas chromatography-mass spectrometry and indirectly as estrogenic potency using an in vitro reporter gene assay (ER, - luc assay). Of the total extractable NP in the sediment, 95% ± 1.5% (mean ± standard error) desorbed quickly into the water phase. By aerobic biodegradation, the total extractable NP concentration and the estrogenic activity were reduced by 97% ± 0.5% and 94% ± 2%, respectively. The easily biodegradable fraction equals the potential bioavailable fraction. Only 43 to 86% of the estrogenic activity in the total extractable fraction, as detected in the ER, - luc assay, could be explained by the present NP concentration. This indicates that other estrogenic compounds were present and that their bioavailability and aerobic degradation were similar to that of NP. Therefore, we propose to use NP as an indicator compound to monitor estrogenicity of this Ebro River sediment. To what extent this conclusion holds for other river sediments depends on the composition of the contaminants and/or the nature of these sediments and requires further testing. [source] Effect of organic carbon content, clay type, and aging on the oral bioavailability of hexachlorobenzene in rats,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2007Shakil A. Saghir Abstract Bioavailability of lipophilic chemicals is influenced by the physicochemical properties of soils/sediment such as particle size, pH, clay, and organic carbon content. The present study investigated the effects of sediment composition and aging on the oral bioavailability of hexachlorobenzene (HCB) in rats. Formulated sediments were prepared using various ratios of kaolinite and montmorillonite clay, sand, peat moss, and black carbon, spiked with 14C-HCB, and orally administered to rats prior to and after one year of aging in dark at 10°C. In the nonaged sediments there was a 21 to 45% reduction in the oral bioavailability of HCB when compared to the corn oil standard without any clear pattern of the impact of the sediment clay and/or organic carbon content. One year of aging resulted in statistically significant (p = 0.049) reduction in the oral bioavailability of HCB from the sediments compared to the corn oil standard and nonaged sediment indicating stronger interactions between HCB and sediment contents with aging. The mean reduction in oral bioavailability after one year of aging ranged from approximately 5 to 14% greater than that observed for nonaged sediments. The fecal elimination of the HCB-derived radioactivity from the one-year-aged sediments was much higher than the nonaged sediments, consistent with the lower absorption from the gastrointestinal tract due to lower desorption of HCB from the aged sediments. Increase in the fecal elimination and decrease in oral bioavailability of 14C-HCB was related to the increase in clay and black carbon. [source] Bioavailability and microbial adaptation to elevated levels of uranium in an acid, organic topsoil forming on an old mine spoilENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Erik Jautris Joner Abstract An old mine spoil at a 19th-century mining site with considerable residues of uranium (400,800 mg U/kg) was investigated with respect to U concentrations in soil and plants and tolerance to U in the soil microbial community in order to describe the bioavailability of U. Measurements of soil fractions representing water-soluble U, easily exchangeable U, and U bound to humified organic matter showed that all fractions contained elevated concentrations of U. Plant U concentrations were only 10 times higher at the mine spoil site compared to the reference site (3 mg U/kg vs 0.3 mg U/kg), while the most easily available soil fractions contained 0.18 to 0.86 mg U/kg soil at the mine spoil. An ecotoxicity bioassay using incorporation of [3H]thymidine into the indigenous microbial communities of the two soils in the presence of increasing U concentrations showed that microorganisms at the mining site were sensitive to U but also that they had acquired a substantial tolerance toward U (EC50, the effective concentration reducing activity by 50% of UO2 -citrate was , 120 ,M as compared to 30 ,M in the reference soil). In the assay, more than 40% of the microbial activity was maintained in the presence of 1 ,M UO2-citrate versus 3% in the reference soil. We conclude that U-enriched mining waste can contain sufficiently elevated concentrations of bioavailable U to affect indigenous microorganisms and that bioavailable U imposes a selection pressure that favors the development of a highly uranium-tolerant microbial community, while plant uptake of U remains low. [source] Indices for bioavailability and biotransformation potential of contaminants in soilsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2004Washington J. Braida Abstract Bioavailability is an important consideration in risk assessment of soil contaminants and in the selection of appropriate remediation technologies for polluted sites. The present study examined the bioavailability and biodegradation potential of phenanthrene with respect to a pseudomonad in 15 different soils through separate measurements of mineralization, transformation, and desorption to a polymeric infinite sink (Tenax®) after 180-d sterile pre-equilibration with phenanthrene. Fractions strongly resistant to desorption and mineralization at long times were evident in all cases. After correcting for bioconversion (moles mineralized per mole transformed) determined in aqueous particle-free soil extracts, a correlation was found between the biotransformation-resistant fraction and the Tenax desorption-resistant fraction. Indices are proposed to assess bioavailability (BAt) and biotransformation potential (BTPt) of a compound in a soil based on parallel desorption and degradation studies over a selected period t. The BAt is the ratio of moles biotransformed to moles desorbed to an infinite sink, and it reflects the biotransformation rate relative to the maximal desorption rate. Values of BA30 (30-d values) ranged from 0.64 (for dark gray silt loam) to 1.12 (Wurtsmith Air Force Base [AFB] 2B, Oscoda, MI, USA). The BTPt is the ratio between moles biotransformed and moles of contaminant remaining sorbed after maximal desorption. The BTPt provides an indication of the maximum extent of biotransformation that may be expected in a system, assuming desorption is a prerequisite for biodegradation. Values of BTP30 ranged between 0.3 (Wurtsmith AFB 1B) and 13 (Mount Pleasant silt loam, NY, USA). The combination of BAt and BTPt provides insights regarding the relationship between physical availability (desorption) and biological processes (biotransformation kinetics, toxicity, other soil factors) that occur during biodegradation and are suggested to represent the remediation potential of the chemical. The BA30 values less than 0.9 and BTP30 values less than five indicate poor potential for site remediation. [source] Studies on bioremediation of polycyclic aromatic hydrocarbon-contaminated sediments: Bioavailability, biodegradability, and toxicity issuesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2003Henry H. Tabak Abstract The widespread contamination by polycyclic aromatic hydrocarbons (PAHs) has created a need for cost-effective bioremediation processes. This research studied a chronically PAH-contaminated estuarine sediment from the East River (ER; NY, USA) characterized by high concentrations of PAHs (,4,190 ppm), sulfide, and metals and a marine sediment from New York/New Jersey Harbor (NY/NJH; USA) with only trace quantities of PAHs (0.1,0.6 ppm). The focus was to examine the relationship between bioavailability of PAHs and their biological removal in a slurry system. Freshwater and marine sediment toxicity tests were conducted to measure baseline toxicity of both sediments to amphipods, aquatic worms, fathead and sheepshead minnow larvae, and a vascular plant; to determine the cause of toxicity; and to evaluate the effectiveness of the biotreatment strategies in reducing toxicity. Results showed the ER sediment was acutely toxic to all freshwater and marine organisms tested and that the toxicity was mainly caused by sulfide, PAHs, and metals present in the sediment. In spite of the high toxicity, most of the PAH compounds showed significant degradation in the aerobic sediment/water slurry system if the initial high oxygen demand due to the high sulfide content of the sediment was overcome. The removal of PAHs by biodegradation was closely related to their desorbed amount in 90% isopropanol solution during 24 h of contact, while the desorption of model PAH compounds from freshly spiked NY/NJH sediment did not describe the bioavailability of PAHs in the East River sediment well. The research improves our understanding of bioavailability as a controlling factor in bioremediation of PAHs and the potential of aerobic biodegradation for PAH removal and ecotoxicity reduction. [source] Partitioning, bioavailability, and toxicity of the pyrethroid insecticide cypermethrin in sedimentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2002Steve J. Maund Abstract The partitioning, bioavailability, and toxicity of cypermethrin in water,sediment systems was investigated. Cypermethrin adsorbed extensively and rapidly, with an overall mean organic carbon (OC) adsorption partition coefficient (Koc) of 350,000, and approximately 99% adsorption occurred within 24 h. Bioavailability was measured via body burdens of Daphnia magna and Chironomus tentans. Mean biota,sediment accumulation factors (BSAFs), that is, the concentration in the organism as a proportion of the concentration in the sediment, decreased with increasing OC content. The BSAF values were 0.31, 0.14, and 0.08 for D. magna and 0.63, 0.19, and 0.08 for C. tentans, in 1, 3, and 13% OC sediments, respectively. The 10-d median lethal sediment concentrations (LC50s) of cypermethrin were 3.6, 18, and 32 mg/kg for Hyalella azteca and 13, 67, and 62 mg/kg for C. tentans in 1, 3, and 13% OC sediments, respectively. Predictions of aqueous concentrations at the LC50 in sediments (based on Koc) compared well to each other and to effect concentrations from studies in water alone, suggesting that equilibrium partitioning theory could be used reasonably to predict and normalize the toxicity of cypermethrin across sediments of differing OC content. [source] Bioavailability of Interferon-beta in patients with multiple sclerosis , fishing for the surrogateEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010B. C. Kieseier No abstract is available for this article. [source] Unexpected Tethering in the Synthesis of Methyl-Substituted Acetyl-1-oxaspiro[4.5]decanes: Novel Woody,Ambery Odorants with Improved Bioavailability,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2008Philip Kraft Abstract To study the olfactory properties of spirocyclic analogs of Iso Gamma (3) with improved water solubility and bioavailability, it was envisaged to spiroannulate 1-acetyl-1,2-dimethylcyclohexanone at the 4-position with a 3,3-dimethyltetrahydrofuran-2-yl moiety that would mimic the polarity of the double bond by its ether function. 3,3-Dimethyl-4-methylenehex-5-en-1-ol (9) was prepared by copper(I)-mediated 1,4-conjugate addition of the Grignard reagent of chloroprene (7) to 3-methylbut-2-enal with subsequent LAH reduction. However, the Diels,Alder reaction of diene 9 with (E)-3-methylpent-3-en-2-one in the presence of Me2AlCl unexpectedly provided exclusively the undesired meta adduct 10, as was discovered after cyclization to 11 with MeSO3H. The wrong selectivity was due to a tethering effect of the Lewis acid, and this could be evaded by changing the carbonyl function of the dienophile to a hydroxy group. Thereby the (5,R*,7,S*,8,S*)-configured 1-(4,,4,,7,,8,-tetramethyl-1,-oxaspiro[4.5]decan-7,/8,-yl)ethan-1-ones 11 and 14, as well as the like -configured 1-(4,,4,,7,-trimethyl-1,-oxaspiro[4.5]decan-7,/8,-yl)ethan-1-ones 16 and 19, were prepared selectively and studied for their odor characters, threshold values, and octanol/water partition coefficients. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Bioavailability of backbone cyclic PK/PBAN neuropeptide antagonists , inhibition of sex pheromone biosynthesis elicited by the natural mechanism in Heliothis peltigera femalesFEBS JOURNAL, Issue 4 2010Aliza Hariton The bioavailability (i.e. ability to penetrate the insect cuticle, to reach the target organ and to exert bioactivity) of two backbone cyclic (BBC) pyrokinin/pheromone biosynthesis-activating neuropeptide (PK/PBAN) antagonistic peptides was tested by applying them topically to Heliothis peltigera females and monitoring the resulting inhibition of sex pheromone production elicited by the natural (endogenous) mechanism during scotophase. Peptides were applied at various time points before the onset of scotophase, in aqueous or organic solvents, and pheromone content was examined at the 5th or 6th hour of scotophase. Both peptides penetrated the cuticle very efficiently and inhibited sex pheromone biosynthesis elicited by the natural mechanism for up to 8 or 9 h after application. The degree of inhibition differed between solvents: those applied in double-distilled water (DDW) were more active than those applied in dimethylsulfoxide (inhibition by 53,73% and 15,38%, respectively, for BBC-25, and 46,67% and 36,40%, respectively for BBC-28). Peptides applied in dimethylsulfoxide and hexane exhibited slightly more persistent inhibitory activity than those applied in DDW. The solvents themselves did not affect sex pheromone production. Multiple applications (at ,2, 0, +2 and +4 h) resulted in almost complete (87%) inhibition of sex pheromone biosynthesis, compared with 52% inhibition following a single application. The present study is the first demonstration of the ability of topically applied PK/PBAN antagonists to inhibit sex pheromone biosynthesis elicited by the natural mechanism in female moths, and provides important information on the bioavailability of BBC peptides and the mechanism responsible for sex pheromone production in these insects. [source] Exposure modeling on a river basin scale in support of risk assessment for chemicals in european river basinsINTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 1 2009Jos van Gils Abstract Following the 2000 European Water Framework Directive and recent insights into sediment management on a river basin scale, we discuss in this paper an exposure model aiming to support a risk assessment for chemicals on a basin-wide scale. It establishes spatial relations between causes (pollution sources) and effects (ecological risk), taking into account the geometry, hydrology, and fine sediment dynamics of European river basins. The model, called EXPOBASIN, explicitly takes into account the interaction of chemicals with fine sediment particles, which is important for many policy-relevant chemicals, such as trace metals and polycyclic aromatic hydrocarbons, and it addresses the potential release of historically polluted sediments as a result of extreme floods, which is a major concern in different European river basins. Bioavailability and bioaccumulation are included in the assessment. As a result, the exposure can be quantified not only in terms of water concentrations, but also in terms of sediment concentrations and concentrations in biota. The primary question to be answered by EXPOBASIN is how chemicals, pollution sources, or both rank quantitatively and objectively on a basin-wide scale. Near the end of 2009, the tool will become available to all European water managers and their technical advisors, as a result of the European Union 6th Framework Programme project MODELKEY The calibration and validation of EXPOBASIN has only just started and will be completed in 2008/2009. Applications to 3 case study areas are planned in this respect. This paper presents the key building blocks of EXPOBASIN and shows some sample results illustrating the raking of pollution sources and chemicals. At the end of the paper, some perspectives for future developments are outlined. [source] Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2002Thierry Buclin Abstract Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 ,g of SCT orally, a placebo, and a 10-,g (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5,1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 ,g exceeding those of 10 ,g intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases. [source] Design of Nano-Laminated Coatings to Control Bioavailability of Lipophilic Food ComponentsJOURNAL OF FOOD SCIENCE, Issue 1 2010David Julian McClements ABSTRACT:, There is currently a lack of effective delivery systems to encapsulate, protect, and release bioactive lipophilic components, such as ,-3 fatty acids, conjugated linoleic acid, tributyrin, vitamins, antioxidants, carotenoids, and phytosterols, which is holding back the development of functional foods designed to combat diseases such as coronary heart disease, diabetes, hypertension, and cancer. Delivery systems consisting of lipid droplets encapsulated by nano-laminated biopolymer coatings have great potential for use in the food industry for the encapsulation, protection, and release of bioactive lipids. This article reviews the potential impact of the physicochemical characteristics of nano-laminated biopolymer coatings on the bioavailability of encapsulated lipids. The effects of layer thickness, composition, electrical charge, permeability, and environmental responsiveness on digestion, release, and absorption of lipophilic components are highlighted. The possibility of designing nano-laminated biopolymer coatings to increase, decrease, or control the bioavailability of encapsulated lipids is shown. Data generated from,in vitro,digestion models and animal feeding studies are presented. This knowledge could be used by the food industry to produce functional foods designed to improve human health and wellness. [source] A Soybean Cultivar Lacking Lipoxygenase 2 and 3 Has Similar Calcium Bioavailability to a Commercial Variety Despite Higher Calcium Absorption InhibitorsJOURNAL OF FOOD SCIENCE, Issue 3 2008H.S.D. Martino ABSTRACT:, The aim of this study was to evaluate calcium bioavailability of a new soybean variety without 2 lipoxygenases with better taste and flavor than a commercial variety containing all 3 isozymes. Using the femur 45Ca uptake method, calcium absorption from a new Brazilian variety, UFV-116, was compared to a common Brazilian variety, OCEPAR 19. Male Sprague,Dawley growing rats weighing 150 to 170 g (10/group) received test meals of whole fat soy flour prepared from UFV-116 or OCEPAR-19 seeds labeled with 10 ,Ci of 45Ca. Femurs were removed after 48 h for determination of 45Ca uptake. Calcium fractional absorption was equivalent between the 2 varieties. The higher oxalate:calcium molar ratio and the higher content of oxalate and phytate (P < 0.05) found in the UFV-116 variety did not affect calcium absorption. Therefore, the new variety is a comparable source of high bioavailable calcium. [source] Prebiotics and Iron Bioavailability,Is There a Connection?JOURNAL OF FOOD SCIENCE, Issue 5 2005Chi Kong Yeung ABSTRACT: Poor bioavailability of dietary iron, especially from diets rich in cereals and legumes, is a major factor contributing to the high prevalence of nutritional iron deficiency in developing countries. Dietary modification to increase intake of components that promote iron absorption from low-bioavailability meals is an effective strategy for combating nutritional iron deficiency. Prebiotics are nondigestible oligosaccharides that selectively stimulate the growth and activity of specific species of bacteria in the colon with benefits to human health. Common prebiotics such as inulin and fructooligosaccharides occur naturally in a wide variety of plant-based foods and have recently been suggested to have an enhancing effect on iron absorption. The hypothesis that prebiotics enhance iron absorption is biologically plausible because fermentation of prebiotics by natural microflora present in the colon may decrease the pH of the luminal content, promote reduction of Fe(III) to Fe(II), stimulate proliferation of epithelial cells to expand the absorptive surface area, and potentially stimulate expression of mineral-transport proteins in epithelial cells. However, data available in the literature characterizing the enhancing properties of prebiotics on iron absorption are inconsistent, and mechanisms of actions involved are poorly understood. The notion that the colon can function as a significant site of iron absorption in response to stimulation by prebiotics, and the effect of long-term exposure to prebiotics on the iron status of iron-deficient subjects remain to be clarified. This review discusses the functional properties of prebiotics as a promising dietary factor that enhances iron absorption. Keywords: prebiotics, iron, colon, oligosaccharides, inulin [source] Bioavailability of generic ritonavir and lopinavir/ritonavir tablet products in a dog modelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2010Kevin W. Garren Abstract In this study, we explored the bioavailability in dogs and chemical potency of generic ritonavir and lopinavir/ritonavir tablet products manufactured by various pharmaceutical companies. Chemical potency of the products was examined by HPLC quantitation of ritonavir and lopinavir. Using a dog model, we determined point estimates for Cmax and AUC of ritonavir and lopinavir/ritonavir for eight generic products compared to Abbott's Norvir® capsule and Kaletra® tablet. Chemical potencies ranged from 79.0% to 104.6%. Point estimates for AUC in the generic tablet products ranged from 0.01 to 1.11, indicating that the relative bioavailability of these formulations was in the range of 1,111% compared to the branded products. This study showed significant variability in bioavailability in a dog model amongst generic tablet products containing the protease inhibitors ritonavir or lopinavir/ritonavir. The chemical potency of the generic products was not indicative of the plasma levels of ritonavir or lopinavir that were achieved. These results reinforce the need for human bioequivalence testing of generic products containing ritonavir or lopinavir/ritonavir to assure that efficacy in patients is not compromised prior to these products being made available to patients. Procurement policies of funding agencies should require such quality assurance processes. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:626,631, 2010 [source] Bioavailability and pharmacokinetic model for ritonavir in the ratJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2007R. Lledó-García Abstract The aim of this study is to investigate in vivo the oral bioavailability of ritonavir and to evaluate the pharmacokinetic model that best describes the plasma concentration behavior after oral and intravenous administration. Male Wistar rats were intravenously administered at 3 mg dose of pure ritonavir and oral administered at 4.6,±,2.5 mg of diluted Norvir®. Blood samples were taken by means of the jugular vein for a 24 h period of time. An analytical high-performance liquid chromatography (HPLC) technique was developed in order to quantify ritonavir plasma concentrations. A nonlinear modeling approach was used to estimate the pharmacokinetic parameters of interest. Results showed that a two-compartmental model with zero-order kinetic in the incorporation process of ritonavir into the body better fitted intravenous and oral data. The estimated oral bioavailability by means of noncompartmental and compartmental approaches resulted in 74% and 76.4%, respectively. These values confirm the ones obtained by other authors in the rat. In conclusion, a zero-order kinetic in the incorporation process at the administered doses suggests the saturation of the possible specialized transport mechanisms involved in the incorporation of ritonavir into the body. These results could justify the use of low doses of ritonavir when improving the bioavailability of other protease inhibitors (PIs) is required. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Formulation and food effects on the oral absorption of a poorly water soluble, highly permeable antiretroviral agentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2002Bruce J. Aungst Abstract DPC 961 is a low-solubility, high-permeability, second-generation non-nucleoside reverse transcriptase inhibitor. The purpose of these studies was to evaluate the effects of drug substance and formulation variables on DPC 961 oral absorption, and to compare fed and fasted state oral absorption. To accomplish this, groups of four to six dogs were dosed with various formulations of DPC 961 under fasted or fed conditions, and DPC 961 pharmacokinetics were examined. Absolute oral bioavailability, based on i.v. AUC in the same dogs, was 24% after a suspension dose in fasted dogs and was 51% in fed dogs. Bioavailability with an unoptimized tablet formulation was 30% in fasted dogs and 86% in fed dogs. DPC 961 oral absorption was shown to be dependent on drug substance particle size in fasted dogs, after dosing with a tablet formulation where only the drug substance particle size was varied, but there was no difference in fed dogs. AUC and Cmax increased in proportion with increases in tablet strength from 100 to 400 mg, using tablets manufactured from a common granulation. Tablets made with 50 and 66% drug loadings showed similar relative oral bioavailabilities. Tablets prepared with two different polymorphic forms of DPC 961 were also compared, and these were found to be equivalent. These studies provided a useful component of the formulation development process, to help identify and control the variables affecting oral absorption of this potential new therapeutic agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1390,1395, 2002 [source] Bioavailability and efficacy of antisense morpholino oligomers targeted to c- myc and cytochrome P-450 3A2 following oral administration in ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002Vikram Arora Abstract Antisense phosphorodiamidate Morpholino oligomers (PMO) are resistant to degradation by cellular hydrolases, DNases, RNases, and phosphodiesterases, but remain sensitive to prolonged exposure to low pH. The present studies evaluate the oral fractional bioavailability, stability, and efficacy of two distinct PMO sequences targeted to c- myc and cytochrome P-450 (CYP) 3A2. The c- myc antisense 20-mer, AVI-4126 (5,-ACGTTGAGGGGCATCGTCGC-3,), slowed the regenerative process in the rat liver after a 70% partial hepatectomy (PH). Rats were administered 3.0 mg/kg AVI-4126 in 0.1 mL saline via a bolus intravenous injection or in 0.5 mL sterile phosphate-buffered saline via gavage immediately following PH. The areas under the plasma concentration versus time curves revealed a fractional oral availability of 78.8% over a period of 10 min through 24 h. Immunoblot analysis of liver tissue from rats treated orally with AVI-4126 demonstrated a sequence-specific reduction in the target protein c-Myc, as well as secondary proliferation markers: proliferating cell nuclear antigen (PCNA), cyclin D1, and p53. The CYP3A2 antisense 22-mer AVI-4472 (5,-GAGCTGAAAGCAGGTCCATCCC-3,) caused a sequence-dependent reduction of approximately five-fold in the rat liver CYP3A2 protein levels and erythromycin demethylation activity in 24 h following oral administration at a dose of 2 mg/kg. It is concluded that oral administration of PMOs can inhibit c- myc and CYP3A2 gene expression in rat liver by an antisense-based mechanism of action. These studies highlight the potential for development of PMOs as orally administered therapeutic agents. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1009,1018, 2002 [source] Aminolevulinic acid-loaded Witepsol microparticles manufactured using a spray congealing procedure: implications for topical photodynamic therapyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2009Rasil Al-Kassas Abstract Objectives The aim was to enhance aminolevulinic acid (ALA) stability by incorporation into low-melting microparticles prepared using a spray congealing procedure and to evaluate temperature-triggered release, allowing topical bioavailability following melting at skin temperature. Methods ALA-loaded Witepsol microparticles were prepared using a novel spray congealing technique. Entrapment efficiency was compared with conventional emulsion-based methods and modelled drug release profiles determined using a membrane separation technique. Raised receiver medium temperature was used to determine triggered release. Bioavailability and lipid-mediated enhancement of ALA penetration were determined in excised murine skin. Key findings ALA-loaded Witepsol microparticles were spherical, with a mean diameter of 20 ,m. Loading and stability studies demonstrated effective encapsulation, ranging from 91% to 100%, with no evidence of degradation to pyrazine derivatives. ALA release correlated with dissolution medium temperature, triggered at temperatures close to that of skin. Results suggested that molten Witepsol enhanced cutaneous permeation, whereas incorporation of microparticles in a semi-solid vehicle attenuated ALA penetration. Optimal use was direct application under occlusion. Conclusions Spray congealing is superior to the emulsion-based procedures with respect to encapsulation efficiency of ALA in Witepsol matrices, providing temperature-triggered release, enhanced stability and improved penetration of ALA through keratinised skin. These features could improve ALA delivery to superficial lesions as part of photodynamic therapy. [source] Improvement of Subcutaneous Bioavailability of Insulin by Sulphobutyl Ether ,-Cyclodextrin in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2000KEIICHI TOKIHIRO The objective of this study was to examine and compare how hydrophilic ,-cyclodextrin derivatives (,-CyDs) improve the bioavailability of insulin following subcutaneous injection of insulin solution in rats. When insulin solutions in the absence of ,-CyDs were injected into the dorsal subcutaneous tissues of rats, the absolute bioavailability of insulin calculated from plasma immunoreactive insulin (IRI) levels was approximately 50%. When maltosyl-,-cyclodextrin was added to the solutions, there was no change in the plasma IRI levels and hypoglycaemia compared with those of the insulin-alone solution. Dimethyl-,-cyclodextrin decreased the bioavailability of insulin, although it increased the maximal concentration of IRI in plasma and the capillary permeability of the fluorescein isothiocyanatedextran 40, a non-degraded permeation marker. When insulin solutions containing sulphobutyl ether-,-cyclodextrin with a degree of substitution of the sulphobutyl group of 3,9 (SBE4-,-CyD) were injected, the IRI level rapidly increased and maintained higher IRI levels for at least 8h. The bioavailability of the insulin/SBE4-,-CyD system was about twice that of insulin alone and approached 96%. The enhancing effects of SBE4-,-CyD may be in part due to the inhibitory effects of SBE4-,-CyDs on the enzymatic degradation and/or the adsorption of insulin onto the subcutaneous tissue at the injection site, although this does not apparently facilitate capillary permeability. These results suggest that SBE4-,-CyD in aqueous insulin injection for subcutaneous administration is useful for improving the bioavailability and the hence the pharmacological effects of insulin. [source] Bioavailability of Ascorbyl-2-Monophosphate to Channel Catfish Fed Purified and Practical DietsJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 2 2002Wendy M. Sealey [source] Bioavailability and pharmacokinetics of florfenicol in broiler chickensJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2003J. Shen The bioavailability and pharmacokinetic disposition of florfenicol in broiler chickens were investigated after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 15 and 30 mg/kg body weight (b.w.). Plasma concentrations of florfenicol were determined by a high performance liquid chromatographic method in which plasma samples were spiked with chloramphenicol as internal standard. Plasma concentration,time data after i.v. administration were best described by a two-compartment open model. The elimination half-lives were 168 ± 43 and 181 ± 71 min, total body clearance 1.02 ± 0.17 and 1.02 ± 0.16 L·kg/h, the volume of distribution at steady-state 4.99 ± 1.11 and 3.50 ± 1.01 L/kg after i.v. injections of 15 and 30 mg/kg b.w., respectively. Plasma concentration,time data after i.m. and oral administrations were adequately described by a one-compartment model. The i.m. bioavailability and the oral bioavailability of florfenicol were 95, 98 and 96, 94%, respectively, indicating that florfenicol was almost absorbed completely after i.m. and oral administrations of 15 and 30 mg/kg b.w. [source] Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2001J. M. B. Musser Eighteen 1-week-old Holstein calves were randomly assigned to one of three groups: (a) sodium penicillin G administered intravenously, (b) sodium penicillin G administered orally, or (c) procaine penicillin G administered orally. All calves were dosed with penicillin G at 4.0 mg/kg BW. At 5 weeks of age, the calves were dosed again. Blood samples were taken serially for 24 h after both dosings. Plasma was assayed for penicillin G by high performance liquid chromatography (HPLC). For i.v. administration, the area under the concentration,time curve (AUC), 7456 and 5508 ng/mL h, and systemic clearance, 0.54 and 0.73 L/kg h, were significantly different (P < 0.05) at 1 and 5 weeks of age, respectively. There were no significant differences between orally administered sodium and procaine penicillin G within the same age groups. Following oral (p.o.) administration, there were significant differences (P < 0.01) at 1 and 5 weeks of age in the AUC, 760 and 409 ng/mL h, terminal half-life, 2.1 and 1.6 h, time of maximum concentration (TMAX), 3.0 and 2.3 h, and maximum plasma concentration (CMAX), 85 and 58 ng/mL, respectively. Bioavailability was 10.2 and 7.4% at 1 and 5 weeks, respectively. [source] Bioavailability of amprolium in fasting and nonfasting chickens after intravenous and oral administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2000Hamamoto The bioavailability of amprolium (APL) was measured after intravenous (i.v.) and oral (p.o.) administration to chickens. Twelve healthy chickens weighing 1.28,1.41 kg received a dose of 13 mg APL/kg intravenously, and 13 or 26 mg APL/kg orally in both a fasted and a nonfasted condition in a Latin square design. Plasma samples were taken from the subwing vein for determination of APL concentration by HPLC method. The data following intravenous and oral administration were best fitted by 2-compartment and 1-compartment models, respectively, using weighted nonlinear least squares regression. The half-life beta t½,, volume of distribution (Vd) and total body clearance (Cl) after intravenous administration were 0.21 h, 0.12 L/kg and 1.32 L/h.kg, respectively. The elimination half-life (t½ Kel) after oral administration was 0.292,0.654 h which is 1.5,3.2 times longer than after intravenous administration, suggesting the presence of a ,flip-flop' phenomenon in chickens. The maximum plasma concentration (Cmax) of 13 mg/kg APL administered orally to chickens during fasting was significantly (about four times) higher than that during nonfasting (P < 0.05). Bioavailability during nonfasting was from 2.3 to 2.6%, and 6.4% during fasting. [source] Clinical trial: comparison of ibuprofen-phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2008F. L. LANZA Summary Background, Chronic use of NSAIDs is associated with gastrointestinal (GI) toxicity that increases with age. Aim, To evaluate the GI safety and therapeutic efficacy of ibuprofen chemically associated with phosphatidylcholine (PC) in osteoarthritic (OA) patients. Methods, A randomized, double-blind trial of 125 patients was performed. A dose of 2400 mg/day of ibuprofen or an equivalent dose of ibuprofen-PC was administered for 6 weeks. GI safety was assessed by endoscopy. Efficacy was assessed by scores of analgesia and anti-inflammatory activity. Bioavailability of ibuprofen was pharmacokinetically assessed. Results, Ibuprofen-PC and ibuprofen provided similar bioavailability/therapeutic efficacy. In the evaluable subjects, a trend for improved GI safety in the ibuprofen-PC group compared with ibuprofen that did not reach statistical significance was observed. However, in patients aged >55 years, a statistically significant advantage for ibuprofen-PC treatment vs. ibuprofen in the prevention of NSAID-induced gut injury was observed with increases in both mean Lanza scores and the risk of developing >2 erosions or an ulcer. Ibuprofen-PC was well tolerated with no major adverse events observed. Conclusion, Ibuprofen-PC is an effective osteoarthritic agent with an improved GI safety profile compared with ibuprofen in older OA patients, who are most susceptible to NSAID-induced gastroduodenal injury. [source] Orthotopic liver transplantation using low-dose tacrolimus and sirolimusLIVER TRANSPLANTATION, Issue 8 2001Vivian C. McAlister MB Although sirolimus (SRL) binds the immunophilin FK506-binding protein-12 (FKBP-12) with greater avidity than tacrolimus (TAC), animal studies have shown that SRL and TAC act synergistically to prevent rejection. Dose-related toxicity is more often the cause of TAC discontinuation than rejection. We hypothesized that SRL would allow for a substantial reduction in the concomitant dose of TAC after liver transplantation to levels less than the threshold for toxicity. A series of 56 liver transplant recipients were administered a combination of SRL and TAC (target trough levels, 7 and 5 ng/mL, respectively). Planned weaning of steroids commenced after 3 months. Pharmacokinetic (PK) studies were undertaken. Patient and graft survival were 52 patients (93%) and 51 grafts (91%), with a follow-up of 23 months (range, 6 to 35 months). One episode (1.8%) of hepatic artery thrombosis was seen. The rate of acute cellular rejection was 14%. No extra treatment was administered in 3 of 8 patients, and the other 5 episodes responded to a single course of steroids. Cytomegalovirus infection occurred in 4 patients (7%). Renal function, glucose control, and lipid metabolism are near normal in 47 patients (84%) without additional medication. Steroid elimination is completed in 51 patients (91%). Bioavailability of SRL and TAC varied between transplant recipients, but trough levels strongly correlated with the area under the curve (r2 = 0.82 and r2 = 0.84, respectively). Simultaneous administration did not affect the PK profile of the drugs at this dose. The ratio of trough level to daily dose correlated between SRL and TAC. The synergistic effect seen in animal models also occurs in clinical liver transplant recipients on SRL-TAC combination immunosuppression. A low-dose combination of SRL and TAC should be compared with conventional immunosuppression in a multicenter, randomized, controlled trial. [source] | |||||||||||||||||||||||||||||||||||||