RESUMEN
Remdesivir (RDV) and tenofovir alafenamide (TAF) are prodrugs designed to be converted to their respective active metabolites. Plasma protein binding (PPB) determination of these prodrugs is important for patients with possible alteration of free fraction of the drugs due to plasma protein changes in renal impairment, hepatic impairment, or pregnancy. However, the prodrugs' instability in human plasma presents a challenge for accurate PPB determination. In this research work, two approaches were used in the method development and qualification for PPB assessment of RDV and TAF. For RDV, dichlorvos was used to inhibit esterase activity to stabilize the prodrug in plasma during equilibrium dialysis (ED). The impact of dichlorvos on protein binding was evaluated and determined to be insignificant by comparing the unbound fraction (fu) determined by the ED method with dichlorvos present and the fu determined by an ultrafiltration method without dichlorvos. In contrast to RDV, TAF degradation in plasma is â¼3-fold slower, and TAF stability cannot be improved by dichlorvos. Fit-for-purpose acceptance criteria for the TAF PPB method were chosen, and an ED method was developed based on these criteria. These two methods were then qualified and applied for PPB determinations in clinical studies.
Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Fármacos Anti-VIH , Infecciones por VIH , Profármacos , Humanos , Tenofovir , Fármacos Anti-VIH/uso terapéutico , Unión Proteica , Profármacos/metabolismo , Diclorvos/uso terapéutico , Adenina , Proteínas Sanguíneas/metabolismo , Infecciones por VIH/tratamiento farmacológicoRESUMEN
The non-methane organic compound (NMOC) emission rate is used to assess compliance with landfill gas emission regulations by the United States Environmental Protection Agency (USEPA). A recent USEPA Report (EPA/600/R-11/033) employed a ratio method to estimate speciated NMOC emissions (i.e., individual NMOC emissions): speciated NMOC emissions=measured methane (CH4) emission multiplied by the ratio of individual NMOCs concentration relative to CH4 concentration (C(NMOCs)/C(CH4)) in the landfill header gas. The objectives of this study were to (1) evaluate the efficacy of the ratio method in estimating speciated NMOC flux from landfills; (2) determine for what types of landfills the ratio method may be in error and why, using recent field data to quantify the spatial variation of (C(NMOCs)/C(CH4)) in landfills; and (3) formulate alternative models for estimating NMOC emissions from landfills for cases in which the ratio method results in biased estimates. This study focuses on emissions through landfill covers measured with flux chambers and evaluates the utility of the ratio method for estimating NMOC emission through this pathway. Evaluation of the ratio method was performed using CH4 and speciated NMOC concentration and flux data from 2012/2013 field sampling of four landfills, an unpublished landfill study, and literature data from three landfills. The ratio method worked well for landfills with thin covers (<40 cm), predicting composite NMOC flux (as hexane-C) to within a factor of 10× for 13 out of 15 measurements. However, for thick covers (⩾40 cm) the ratio method overestimated NMOC emissions by ⩾10× for 8 out of 10 measurements. Alternative models were explored incorporating other chemical properties into the ratio method. A molecular weight squared (MW)(2)-modified ratio equation was shown to best address the tendency of the current ratio method to overestimate NMOC fluxes for thick covers. While these analyses were only performed using NMOC fluxes through landfill covers measured with flux chambers, results indicate the current USEPA approach for estimating NMOC emissions may overestimate speciated NMOC emission ⩾10× for many compounds.
Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Modelos Teóricos , Compuestos Orgánicos/análisis , Instalaciones de Eliminación de Residuos , Estados Unidos , United States Environmental Protection AgencyRESUMEN
An assessment of the risk to human health and the environment associated with the presence of organic contaminants (OCs) in landfills necessitates reliable predictive models. The overall objectives of this study were to (1) conduct column experiments to measure the fate and transport of an OC in a simulated solid waste mixture, (2) compare the results of column experiments to model predictions using HYDRUS-1D (version 4.13), a contaminant fate and transport model that can be parameterized to simulate the laboratory experimental system, and (3) determine model input parameters from independently conducted batch experiments. Experiments were conducted in which sorption only and sorption plus biodegradation influenced OC transport. HYDRUS-1D can reasonably simulate the fate and transport of phenol in an anaerobic and fully saturated waste column in which biodegradation and sorption are the prevailing fate processes. The agreement between model predictions and column data was imperfect (i.e., within a factor of two) for the sorption plus biodegradation test and the error almost certainly lies in the difficulty of measuring a biodegradation rate that is applicable to the column conditions. Nevertheless, a biodegradation rate estimate that is within a factor of two or even five may be adequate in the context of a landfill, given the extended retention time and the fact that leachate release will be controlled by the infiltration rate which can be minimized by engineering controls.
Asunto(s)
Reactores Biológicos , Fenol/metabolismo , Eliminación de Residuos/métodos , Adsorción , Biodegradación Ambiental , Cromatografía Líquida de Alta Presión , Simulación por Computador , Modelos Químicos , Fenol/químicaRESUMEN
Factors controlling organic contaminant sorption to common plastics in municipal solid waste were identified. Consumer plastics [drinking water container, prescription drug bottle, soda bottle, disposable cold cup, computer casing, furniture foam, carpet, vinyl flooring, formica sheet] and model polymers [high-density polyethylene (HDPE), medium-density polyethylene, low-density polyethylene, poly(vinyl chloride) (PVC)] were characterized by X-ray diffractometry, differential scanning calorimetry, and elemental analysis. The material characterization was used to interpret batch isotherm and kinetic data. K(p) values describing toluene sorption to rubbery or "soft" polymers could be normalized by the amorphous polymer fraction (f(amorphous)) but not by the organic carbon fraction (f(oc)). Diffusion coefficients (D) describing the uptake rate of toluene by rubbery plastics (HDPE, drinking water container, prescription drug bottle) were similar (D approximately 10(-10) cm(2)/s), indicating that pure HDPE can be used as a model for rubbery plastics. Toluene diffusivity was similar among glassy or "hard" plastics (PVC, soda bottle, computer casing, disposable cold cup; D approximately 10(-12) cm(2)/s) but lower than for rubbery plastics. Plastics in landfills are potential sinks of hydrophobic organic contaminants (HOCs) because of their higher affinity for HOCs compared to lignocellulosic materials and the slow desorption of HOCs from glassy plastics.
Asunto(s)
Contaminantes Ambientales/química , Movimiento (Física) , Compuestos Orgánicos/química , Plásticos/química , Eliminación de Residuos , Adsorción , Ciudades , Difusión , Interacciones Hidrofóbicas e Hidrofílicas , Tolueno/químicaRESUMEN
Desorption rates of toluene, o-xylene and tetrachloroethene from individual municipal solid waste components [high-density polyethylene (HDPE); poly(vinyl chloride) (PVC); office paper; newsprint; and rabbit food, a model food and yard waste] were determined. Effects of sorbent and sorbate properties, solvent composition (ultrapure water, acidogenic and methanogenic leachates), and contact time ("aging") on desorption rates were evaluated. Hydrophobic organic contaminant (HOC) desorption from PVC and HDPE could be described with a single-parameter polymer diffusion model. In contrast, a three-parameter, biphasic polymer diffusion model was required to describe HOC desorption rates from biopolymer composites. In general, HOC desorption rates from plastics were rapid for HDPE (D = 10(-10) cm(2)/s), a rubbery polymer, but slower for PVC (D = 10(-13)-10(-14) cm(2)/s), a glassy polymer. For biopolymer composites, a large fraction of sorbed HOCs was rapidly released (D(r) = 10(-9)-10(-10) cm(2)/s) while the remaining fraction desorbed slowly (D(s) = 10(-11)-10(-16) cm(2)/s). The toluene desorption rate from PVC was 1 order of magnitude faster in acidogenic leachate than in either ultrapure water or methanogenic leachate, a result that was primarily attributed to the plasticizing effect of volatile fatty acids in acidogenic leachate. For biopolymer composites, small increases in the slowly desorbing HOC fraction were observed with increasing aging time.
Asunto(s)
Eliminación de Residuos , Tetracloroetileno/química , Tolueno/química , Xilenos/química , Contaminantes Ambientales/química , Estructura MolecularRESUMEN
Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2'-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g(-1) to microg g(-1). Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub microg l(-1) to mg l(-1) and were correlated with the level of economic development.