The use of urea fertiliser has been associated with relatively poor nitrogen (N) use efficiency (NUE) due to heavy N losses such as gaseous emissions of ammonia (NH₃) and nitrous oxide (N₂O) and nitrate (NO₃⁻) leaching into surface and ground waters. Improving N use-efficiency of applied urea is therefore critical to maximise its uptake and to minimise its footprint on the environment. The study was conducted under laboratory-glasshouse conditions (Chapter 2-4)and lysimiter-field plot studies (Chapter 5). In chapter 2, Two glasshouse-based experimentswere conducted to investigate the potential of incorporating urea fertiliser with ureaseinhibitor, (N-(n-butyl) thiophosphoric triamide (nBTPT) or ‘Agrotain’) to enhance fertiliser N uptake efficiency. Urea, with or without Agrotain, was applied to Ryegrass (Lolium perenne L.) grown in standard plant trays maintained at soil moisture contents of 75–80% field capacity, at rates equivalent to 25 or 50 kg Nha⁻¹. These treatments were compared with other common forms of N fertilisers (ammonium nitrate, ammonium sulphate and sodium nitrate). In a separate pot experiment, granular ¹⁵N urea (10 atom %) with or without Agrotain, was applied at 25 kg Nh⁻¹ to track N use-efficiency and the fate of ¹⁵N-labelled fertiliser. In both experiments, Agrotain-treated urea improved bioavailability (defined as the fraction of total soil N that can interact with a biological target in the plant or that can be taken up by plant) of added N and resulted in significantly higher herbage DM yield and N uptake than urea alone or other forms of N fertilisers. Results from the ¹⁵N experiment support the suggestion that a delay in urea hydrolysis by Agrotain provided an opportunity for direct plant uptake of an increased proportion of the applied urea-N than in the case of urea alone. In chapter 3, two more glasshouse-based experiments were conducted to investigate if urea applied in fine particle application (FPA), with or without Agrotain, had any effect on fertiliser-N uptake efficiency (defined as the difference in N uptake between the fertiliser treatment and the control as a percentage of the amount of N applied) under optimum soil moisture (75-80% field capacity) and temperature (25 °C) conditions, in comparison with other common forms of N fertilisers applied, either in FPA or in granular form. In a separate pot experiment, ¹⁵N urea (10 atom %), with or without Agrotain, was applied to either shoots or leaves only or to the soil surface (avoiding the shoots and leaves) to determine urea hydrolysis, herbage DM and ¹⁵N uptake. In both experiments, herbage DM yield and N uptake were significantly greater in the FPA treatments than in those receiving granular application. Agrotain-treated urea FPA resulted in significantly higher N response efficiency (difference between the dry matter produced by the various fertiliser treatments and the control, divided by the amount of N applied) than urea FPA alone or other forms of N fertilisers. Results from the ¹⁵N experiment support the idea that Agrotain treatment improves the N response of urea applied in FPA form due to a delay in hydrolysis of urea, thus providing herbage an extended opportunity to absorb added urea directly through leaves, cuticles and roots. A further glasshouse-based study was conducted to investigate the effect of Agrotain and irrigation on urea hydrolysis and its movement in a Typic Haplustepts silt loam soil (Chapter 4). A total of 72 repacked soil cores (140 mm inner diameter and 100 mm deep) were used - half (36) of these cores were adjusted to soil moisture contents of 80% field capacity (FC) and the remaining 36 cores to 50% FC. Granular urea, with or without Agrotain, was applied at a rate equivalent to 100 kg N ha⁻¹. Twelve pots were destructively sampled at each day after 1, 2, 3, 4, 7, and 10 days of treatment application to determine urea hydrolysis and its lateral and vertical movement in different soil layers. Agrotain-treated urea delayed urea hydrolysis compared with urea alone during the first 7 days of its application. This delay in urea hydrolysis by Agrotain enabled added urea to disperse and move away from the surface soil layer to the sub-surface soil layer both vertically and laterally. In contrast, most urea in the absence of Agrotain hydrolysed within 2 days of its application. Irrigation after 1 day resulted in further urea movement from the surface soil layer (0-10 mm) to the sub-soil layer (30-50 mm) in Agrotain-treated urea. These results suggest that Agrotain delayed urea hydrolysis and allowed more time for rainfall or irrigation to move the added urea from the surface layer to sub-soil layers where it is likely to make good contact with plant roots. This distribution of urea in the rooting zone (0-200 mm) has the potential to enhance N use efficiency and minimise N losses via ammonia (NH₃) volatilisation from surface-applied urea. Finally, a field study using lysimeters (300 mm inner diameter and 400 mm deep), and small field plots (1 m² in area) was established using a silt loam Typic Haplustepts soil (Soil Survey Staff 1998) to investigate the effect of FPA and granular applications of urea, with or without Agrotain, on N losses and N use efficiency (Chapter 5). The five treatments were: control (no N) and ¹⁵N-labelled urea (10 atom %), with or without Agrotain, applied to lysimeters or mini plots (un-labelled urea), either in granular form to the soil surface or in FPA form (through a spray) at a rate equivalent to 100 kg N ha⁻¹. Gaseous emissions of NH₃ and N₂O, NO₃⁻ leaching, herbage production, N response efficiency, total N uptake and total recovery of applied ¹⁵N in the plant and soil were determined up to 63 days. Urea-alone and urea with Agrotain, applied in FPA form, was more effective than its granular form and reduced N2O emissions by 5-12% and NO3- leaching losses by 31-55%. Urea-alone applied in FPA form had no significant effect in reducing NH₃ losses compared with granular form. However, urea with Agrotain applied in FPA form reduced NH₃ emissions by 69% compared with the equivalent granular treatment. Urea-alone and with Agrotain applied in FPA form increased herbage dry matter production by 27% and 38%, and N response efficiency compared with the equivalent granular urea application, respectively. Urea applied in FPA form resulted in significantly higher ¹⁵N recovery in the shoots compared with granular treatments – this was improved further when urea in FPA form was applied with Agrotain. Thus, treating urea with Agrotain in FPA under field conditions has the potential to delay its hydrolysis, minimise N losses and improve N use efficiency and herbage production. The lower dry matter production and N-response efficiency to urea applied in FPA form in Chapter 3 are probably because of additional factors such as lower application rates (25 kg N ha⁻¹ ) or lack of interception of urea by the leaves. Applying urea in FPA form is a good management strategy and I conclude that combining FPA urea with Agrotain has the potential to increase N use efficiency and herbage production further.

Graduation date: 1991

Purpose: The aim of this study was to investigate the usefulness of formulation approaches to minimise injection site reactions for poorly soluble drugs. The specific objectives were to modify the injection site reactions by identification of irritant components in the formulation and control of their release kinetics; and to gain understanding of formulation approaches to create a favourable microenvironment in the tissues allowing better tissue tolerance and drug absorption. Methods: Physicochemical properties of the model drug, ricobendazole (RBZ) were characterised using conventional methods. Three formulation approaches to minimise irritancy of the low pH RBZ solution were assessed. An in vitro method using 96-well microplates and a microtiter plate reader was used for detection of drug precipitation on dilution for formulation characterisation. Cellular damage by the formulations was investigated in L929 fibroblasts using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) assays. Tissue tolerance and pharmacokinetics were simultaneously investigated after subcutaneous injection in sheep. A low pH RBZ solution was used as a reference formulation. Results: Preformulation studies showed that RBZ was practically insoluble in water and oils, and was slightly soluble in commonly used co-solvents. Solubility was slightly improved by complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD, K₁:₁ = 311 M⁻�) or a combination of low pH (> 2) with surfactants or co-solvents. A U-shaped pH-solubility profile in aqueous solutions indicated that RBZ is an ampholyte. pKa values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 (basic) and 9.82 and 9.53 (acidic) respectively. The partition coefficient was 14.3 - 15.2 at pH 6 - 9 and less at higher or lower pH. In aqueous solutions, RBZ showed a V-shaped pH-degradation rate profile and was most stable at pH 4.8. Degradation pathways were identified as hydrolysis and oxidation. Three RBZ injectables (5%) were obtained by modification of the low pH RBZ solution; addition of 20% HP-β-CD, incorporation into a w/o emulsion, and a microemulsion (ME). On dilution with SPB, the onset time of drug precipitation was prolonged and the rate was reduced in the presence of HP-β-CD. The w/o emulsion had a low viscosity (< 60 mPa.s) and exhibited Newtonian flow. Drug release versus the square root of time was linear and the release rate could be adjusted by phase ratio and droplet size. Drug release was found to be by diffusion. A coarse emulsion layer appeared at the interface between the ME and buffer. Drug release from the ME was faster than from the emulsion and was linear with the square root of time. On titration into SPB, the three formulations showed controlling effects on the release of H₃O⁺ compared to the reference formulation. RBZ (0.1 mg/ml) was more toxic to L929 cells than the co-solvent propylene glycol (50 mg/ml). The formulations showed greater cytotoxicity than their vehicles in the order: ME > RBZ solution = emulsion > HP-β-CD. HP-β-CD and emulsion excipients showed little or no cytotoxicity. The MEs exhibited more toxicity in the LDH assay than in the MTS assay. A reversed phase HPLC assay for simultaneous determination of RBZ and its metabolite in sheep plasma using an isocratic system with UV detection was developed and used in the pharmacokinetic studies. Plasma samples were prepared by solid phase extraction. A suitable internal standard was selected by quantitative structure-retention relationships analysis. The composition of a ternary mobile phase was optimised with the assistance of multiple linear regression. The assays were linear over the concentration range 10 - 1000 ng/ml for both analytes (r > 0.999) with satisfactory inter-day and intra-day precision and accuracy (CV < 10%). The recoveries for all analytes were > 96%. A pilot study in sheep suggests that injection of the vehicles (the CD, emulsion and ME) caused virtually no pain on injection or site reactions. Both the reference formulation and its vehicle induced pain on injection and resulted in swollen tissues. Histology after two weeks showed granulation for the formulation, but not the vehicle. In contrast, animals showed virtually no injection site reactions with the ME and emulsion. The HP-β-CD formulation gave transient pain on injection but a two-fold increase in bioavailability compared with the reference. The emulsion produced sustained drug release and increased drug absorption. In the main study, the HP-β-CD vehicle showed good tissue compatibility. Irritation by the HP-β-CD formulation was attributed to the low pH. Cmax, tmax and AUC0-[infinity] for the reference formulation were 1.3 � 0.3 [mu]g/ml, 9.6 � 2.9 h and 36.7 � 9.2 [mu]g�h/ml respectively, while the corresponding data for the HP-β-CD formulation were 2.9 � 0.8 [mu]g/ml, 5.0 � 0.6 h and 54.5 � 15.3 [mu]g�h/ml respectively. The half-life following the injection of the HP-β-CD formulation (5.5 � 2.8 h) was shorter than that of the reference formulation (8.5 � 3.4 h). Conclusions: Injection site reactions may be minimised by identification of irritant components in a formulation and by controlling their release. Controlling the burst release of the poorly water soluble drug RBZ in a low pH solution could improve tissue tolerance and minimise post-injection precipitation, and hence increase drug bioavailability. In addition, HP-β-CD was a useful local injectable carrier which significantly enhanced the absorption of RBZ after subcutaneous injection in sheep.

Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Oyelere, Adegboyega; Committee Member: Bunz, Uwe; Committee Member: Collard, David; Committee Member: Lobachev, Kirill; Committee Member: Tolbert, Laren.

Determining accurate exposure estimates and subsequent risk of hydrophobic organic contaminants (HOCs) in aquatic sediments requires measuring the bioavailable and/or bioaccessible concentration in sediment; as total extractable concentrations have not been found to produce accurate results. Organic carbon normalization was originally proposed as a means of accounting for the bioavailable concentration by estimating the chemical activity of the contaminant expressed as the freely dissolved chemical concentration in the interstitial water, thus correcting exhaustive extractable concentrations for the sorbing phase of sediments. Organic carbon normalization often fails, however, to accurately reflect exposure as other environmental variables (i.e. organic carbon composition, aging time of contaminants in the environment) alter desorption, such that changes in chemical activity as represented by the interstitial water concentrations are not controlled by organic carbon alone. Desorption-based samplers, such as single-point Tenax extractions (SPTE), provide a clearer estimate of bioaccessibility than organic carbon normalization by serving as a sink for desorbing compound for the length of the extraction. In this way, SPTEs account for all the factors affecting desorption and the resulting interstitial water concentrations, providing estimates of the chemical concentration that will become available for exposure in a given time frame. The utility of SPTEs as an exposure metric has been demonstrated many times in the literature through estimates of bioaccumulation and development of toxicity benchmarks. The simplicity, accuracy, and robust nature of this technique suggests this tool could serve as an ideal means of evaluating exposure and risk of HOCs, and more specifically acutely toxic compounds, such as pyrethroids, during environmental sampling and risk assessments of aquatic sediments. However, the use of this method is limited within the scientific literature and absent from most risk assessment protocols. The reasons for its limited use are linked to poor methodological standardization, an absence of understanding of environmental and methodological variation on estimates of bioaccessibility provided by SPTEs, and only a vague idea of how Tenax extractions relate to other exposure metrics, such as passive samplers. Therefore, the dissertation goals were to: evaluate the effects of variation in the SPTE, specifically the Tenax mass to organic carbon mass (Tenax:OC) ratio, on exposure estimates of pyrethroids (Chapter Two); understand how methodological and environmental variation affect the relation of SPTEs to bioaccessibility represented by desorption of pyrethroids from the labile desorbing fraction (Frap) (Chapter Three); and, determine how bioavailability and bioaccessibility are linked through evaluation of chemical activity expressed as the freely dissolved chemical concentrations provided by SPTEs, passive sampler concentrations, and Frap (Chapter Four). The most variable aspect of the SPTE within the Tenax literature is the Tenax:OC ratio used during 24 h SPTEs. Yet, no study has evaluated how altering this ratio may affect 24 h SPTE concentrations and thus, biological exposure estimates provided by Tenax extractions. Manipulating the Tenax:OC ratio used during 24 h SPTEs of pyrethroids from laboratory-spiked and field-contaminated sediments revealed the effect of this variation was such that Tenax extractable pyrethroid concentrations varied between 0.85 to 3.91-fold between the highest and lowest ratios examined. The results of this experiment suggest most of the variation in toxicological endpoints derived using Tenax extractable concentrations is due to toxicokinetic and toxicodynamic variation in biological responses across sediments and not due to methodological variation of the Tenax extraction (Chapter Two). The utility of the SPTEs as an estimate of exposure is linked to the ability of SPTEs to reflect the chemical concentration that desorbs from sediment. As many factors, such as the organic carbon content, aging time of sediments, and hydrophobicity of the compounds, can impact desorption, understanding how these factors affect the relationship of SPTEs to biological exposure is needed to evaluate the consistency of the Tenax extraction. The relation of SPTE concentrations to Frap was proportional despite changes in organic carbon content of the sediment being extracted, the hydrophobicity of the pyrethroids, or the Tenax mass used during the extraction, such that the SPTE concentration was equal to 1.46 ± 0.03 times the pyrethroid concentration in Frap (Chapter Three). Only the aging time of the pyrethroids in the sediment significantly affected this relationship, as desorption from longer aged sediments slowed, reducing the 24 h SPTE concentration to Frap ratio by -0.0027/d (Chapter Three). The results of Chapters Two and Three demonstrate the consistency of the Tenax extraction as a representation of biological exposure of pyrethroids in sediment. However, other aspects limit the widespread use of the Tenax method, particularly the relation of this technique to more widely accepted bioavailability-based metrics, such as passives samplers. Tenax extractions are often disregarded in favor of passive samplers as the link between bioavailability-based metrics, chemical activity, and exposure is well understood. However, as SPTEs and passive samplers both demonstrate a clear relation to bioaccessibility through estimates of Frap, it was hypothesized that both exposure metrics represent the same chemical fraction of sediment, and as such could be considered complementary tools for evaluating biological exposure through estimates of the freely dissolved interstitial water concentration. This was confirmed when comparisons of the chemical activity expressed as the interstitial water concentration at equilibrium were done using the chemical concentration estimated by Frap, a passive sampler, and SPTEs. Strong linear relationships (p<0.0001) were found among all three metrics, such that Frap, passive sampler, or 24 h SPTE concentrations of pyrethroids from sediment provide comparable estimates of the freely dissolved interstitial water concentration in sediment. Thus, Tenax extractions and passive samplers, which describe the bioaccessible and bioavailable concentrations, respectively, describe the same chemical fraction in sediment; the labile desorbing fraction. This dissertation provides further concrete evidence that the SPTE offers a robust, rapid, and cost-effective means of evaluating exposure of acutely toxic compounds in sediment. With data that link this exposure metric to more widely accepted methods, such as passive samplers, and demonstrate the robust character of the SPTE, the research presented here should further the use of the SPTE within the scientific and risk assessment communities.

Orientador: Ronilson Agnaldo Moreno / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-05T05:47:22Z (GMT). No. of bitstreams: 1 Maluly_HellenDeaBarros_M.pdf: 7988282 bytes, checksum: 2d5724c0002bc95aaec9c7de5cbd35bd (MD5) Previous issue date: 2005 / Resumo: O Objetivo deste estudo foi comparar a bioequivalência do Cefadroxil - cápsula (500mg) da Apotex do Brasil Ltda (formulação teste) and Cemmox@do Laboratório Bristol-Myers Squibb (formulação de referencia) em voluntários sadios de ambos os sexos. Este estudo foi necessário para comercialização deste medicamento. O estudo foi aleatorizado, cruzado, com dois períodos e duas seqüências (2x2) e com uma semana de intervalo entre as doses (wash out), onde os mesmos voluntários receberam, em cada período a formulação teste e a formulação de referência. A seqüência de tratamento foi determinada por uma lista de aleatorização, automaticamente produzida pela Medicines Clinical Trials Control System. As amostras de plasma foram coletadas num intervalo de 36 horas. As concentrações de Cefadroxil foram analisadas por cromatografia líquida de alta eficiência acoplada a um detector de UV-visível. A partir da curva da concentração de Cefadroxil no plasma vs tempo foram obtidos os parâmetros farmacocinéticos: 'ASC IND. 0-t¿, 'ASC IND. 0-INFINITO¿ e 'C IND. max¿. As médias geométricas de CefadroxiI / 'Cefamox MARCA REGISTRADA¿ 500 mg em porcentagem foram: 105.58% (90% CI=102.17%; 109.10%) para 'ASC IND. 0-t¿, 104.74% (90% CI= 101.55%; 108.02%), para 'ASC IND. 0-INFINITO¿ 112.08% (90% CI=10S.59%; 118.97%) para 'C IND. max¿.Sendo 90% o intervalo de confiança para 'C IND. max¿, 'ASC IND. 0-t¿, 'ASC IND. 0-INFINITO¿ estiverem entre 80-125% do intervalo proposto pela RDC 135 (ANVISA/mai 2003), conclui-se que o Cefadroxil - cápsulas (500 mg) foi bioequivalente ao Cefamox MARCA REGISTRADA¿ ,de acordo com as porcentagens e extensão da absorção / Abstract: The objective of this study is to compare the bioequivalence of Cefadroxil- capsule 500 mg ¿ formulated by Apotex of Brazil Ltda (test formulation) and Cefamox by LaboratoryBristol-Myers Squibb (reference formulation) in volunteers of both sexes. This study was necessary for the commercialization of medicines. The study was conducted with a randomized two-period crossover design (2x2) and a one-week washout period, the same volunteers received, in each period, a test formulation or a reference formulation. The treatment sequence was determined by a randomization list, automatically produced by Medicines Clinical Trials Control System. Plasma samples were obtained over a 36-hour interval. Cefadroxil concentrations were analyzed by combined high pressure liquid chromatography and UV-visible detection (HPLC-UV). From the Cefadroxil plasma concentration vs time curves the following pharmacokinetic parameters were obtained: 'AUC IND. 0-t ', 'AUC IND. 0-INFINITO¿ and 'C IND. max¿. The Geometric mean of Cefadroxil / Cefamox 500 mg for individual percentage ratio was 105.58% (90% CI=102.17%; 109.10%) for an area under the cefadroxil plasma concentration versus time curves (0-t), 104.74% (90% CI= 101.55%; 108.02%), for an area under the cefadroxil plasma concentration versus time curves ('0-INFINITO¿), and 112.08% (90% CI=105.59%; 118.97%) for maximum observed plasma concentration. Conclusion: Since 90% CI for both 'C IND. max¿, 'AUC IND. 0-t ', and 'AUC IND. 0-INFINITO¿ were within the 80-125% interval proposed by the RDC 135 (ANVISA/may 2003), it was conc1uded that Cefadroxil - capsule 500 mg was bioequivalent to Cefamox, according to both the rate and the extension of absorption / Mestrado / Mestre em Farmacologia

Orientador: Gilberto de Nucci / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T13:53:54Z (GMT). No. of bitstreams: 1 Oliveira_LinaSayuriOdoBuenode_M.pdf: 1845448 bytes, checksum: 4fea923152025c316ca4c99487b21970 (MD5) Previous issue date: 2008 / Resumo: Betametasona é um corticosteróide sintético designado para exercer a função de um glicocorticóide ativo. Como um álcool livre, betametasona apresenta uma vasta aplicação clínica com atividade antiinflamatória e imunossupressora. A betametasona foi extraída com 0,5mL de plasma humano por extração líquido-líquido (ELL) utilizando Cloranfenicol como padrão interno. O método utilizou uma corrida cromatográfica de 2,5min, com a coluna analítica C18 (100mm×2.1mm i.d.), a calibração da curva linear de 0,05ng/mL a 50ng/mL (r2 > 0,993). A exatidão inter-corrida dos controles de qualidade foi 92.3% (CQA 0.15ng/mL), 90.7% (CQB 4.0ng/mL) e 97.2% (CQC 40ng/mL). A precisão inter-corrida dos controles de qualidade foi 8.7% (CQA 0.15ng/mL), 9.0% (CQB 4.0ng/mL) e 9.8% (CQC 40ng/mL). O método aqui descrito foi empregado em estudo de biodisponibilidade relativa de duas formulações contendo dexclorfeniramina/betametasona 2mg/0.25mg comprimido. A razão da média geométrica e dos respectivos intervalos de confiança (IC) de Betametasona/Celestamine® foram 107.61% (101.62-113.95%) para AUClast, 106.93% 102.08-112.00% para AUC0-inf e 105.06% (96.56-114.31%) para Cmax. O intervalo deconfiança de 90% calculado para a razão individual das médias de Cmax, ASC0-72h, ASClast e ASC0-inf para betametasona/celestamine® estavam dentro do intervalo de 80- 125% definido pela Agência Vigilância Sanitária (ANVISA). No presente estudo um método, rápido, sensível e robusto foi desenvolvido para a determinação e quantificação de betametasona em plasma humano através da cromatografia líquida acoplada a espectrometria de massas usando fotoionização à pressão atmosférica em modo negativo. / Abstract: Betamethasone is a synthetic corticosteroid designed to exert a marked glucocorticoid activity. As the free alcohol, betamethasone finds widespread clinical applications related to its anti-inflammatory and immunosuppressant activity. Betamethasone was extracted from 0.5 ml human plasma by liquid-liquid extraction (LLE) using chloramphenicol as internal standard. The method has a chromatographic run of 2.5 min using a C18 analytical column (100mm×2.1mm i.d.) and the linear calibration curve over the range was linear from 0.05 to 50 ng ml-1 (r2 > 0.993). The between-run accuracy, based on the relative standard deviation replicate quality controls was 92.3% (0.15 ng ml-1), 90.7% (4.0 ng ml-1) and 97.2% (40 ng ml-1). The between-run precision for the above-mentioned concentrations was 8.7, 9.0 and 9.8%, respectively. The method herein described was employed in a bioequivalence study of two formulations of dexchlorpheniramine/betamethasone 2 mg/0.25 mg tablets. The geometric mean and respective 90% confidence interval (Cl) of betamethasone/Celestamine® percent ratios were 107.61% (101.62-113.95%) for AUClast, 06.93% 102.08-112.00%for AUC0-inf and 105.06% (96.56-114.31%) for Cmax. In adition, the calculated 90% Cl for mean Cmax, AUClast and AUCinf betamethasone/celestamine® individual ratios were within the 80-125% interval defined by the Agência Vigilância Sanitária - ANVISA. In the present study, a fast, sensitive, robust method was developed for the determination and quantification of betamethasone in human plasma by liquid chromatography coupled with tandem mass spectrometry, using photospray ionization in negative mode. / Mestrado / Mestre em Farmacologia

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O tratamento de escolha para o hipotireoidismo à a levotiroxina sÃdica. Estudos de biodisponibilidade com medicamentos com caracterÃsticas hormonais tÃm grande importÃncia na garantia do controle da qualidade dos fÃrmacos disponÃveis à populaÃÃo. Logo, o objetivo deste estudo foi: Determinar a biodisponibilidade de duas formulaÃÃes de 150 &#956;g de levotiroxina sÃdica em indivÃduos sadios; apÃs Ãnica administraÃÃo de 600 &#956;g, por via oral e comparÃ-las .A pesquisa consistiu de um estudo aberto, randomizado, cruzado, com dois tratamentos, dois perÃodos (duas seqÃÃncias), nos quais os 24 voluntÃrios, saudÃveis e de ambos os sexos, receberam, em cada perÃodo distinto, a formulaÃÃo teste do Achà LaboratÃrios FarmacÃuticos S.A. ou a formulaÃÃo referÃncia da Sanofi-Synthelabo Ltda. (Puran ÂT4). Foi utilizado o imunoensaio de eletroquimioluminescÃncia para dosar as concentraÃÃes dos hormÃnios T3 (liotironina) e T4 (levotiroxina) nas amostras de soro dos voluntÃrios e posterior determinaÃÃo dos parÃmetros farmacocinÃticos. Os resultados da anÃlise de variÃncia (ANOVA) da Levotiroxina demonstraram um significante efeito de perÃodo com diminuiÃÃo dos nÃveis sÃricos do T4, no segundo internamento, independente da aleatorizaÃÃo (p<0,05). As razÃes das mÃdias geomÃtricas do Cmax e ASC0-48h das formulaÃÃes teste e referÃncia foram 92,97% e 97,87%, respectivamente. Os intervalos de confianÃa de 90% foram de 88,70â 97,44% e 93,10 - 102,88%, respectivamente. As formulaÃÃes de comprimidos de 150microg de levotiroxina sÃdica estudadas apresentaram biodisponibilidades semelhantes, quando administradas em dose Ãnica de 600microg, por via oral a voluntÃrios sadios; sendo entÃo consideradas bioequivalentes.

South Africans frequently consume red meat as part of their diet. However the nutrient content of South African sheep meat is derived from other countries. The Red Meat Industry considered it essential to have more reliable data and thus the nutrient content of A2 South African lamb was recently determined and published. This is the next phase of the study in which the right sides of C2 mutton carcasses were used to determine the nutrient and physical (carcass) composition of each raw cut as well as the whole carcass by calculation. Eighteen mutton carcasses of the most commonly consumed breeds, namely Dorper and Merino, in South Africa were selected. The carcasses were obtained from large abattoirs form three mutton producing regions in South Africa namely Ermelo, the Karoo and Kalahari. Chilled carcass sides were subdivided into ten primal cuts. Three cuts (shoulder, loin and leg) from the left side were cooked in order to determine the nutrient composition thereof. The cuts were dissected into meat which consists of muscle and intramuscular fat, intermuscular - plus subcutaneous fat and bone in order to determine the physical composition per cut and for the whole carcass. Meat compromise of 63.2% of the carcass, with bone contributing to 20.5% and fat to 16.9%. Results showed differences in the physical composition of South African C2 mutton as it contains on average 47% less fat and 19% more lean muscle, when compared to previous published composition data. Three cuts (shoulder, loin and leg) from the left side were cooked in order to determine the nutrient composition thereof. Cooking resulted in an increase in the protein and cholesterol concentrations of the cooked cuts. Iron content was higher in the cooked loin and leg but decreased in the cooked shoulder. According to nutrient density, a 100g edible portion of the leg, loin and shoulder have a nutrient density higher than one for protein, iron, zinc and vitamin B12 indicating that these cuts are a good source of these specific nutrients. A 100g edible portion of the loin cut contained higher fat quantities than the cooked shoulder and leg cuts. The loin cut also had a higher cholesterol content at 70.8mg compared the 58.5mg cholesterol content in the shoulder and 57.9mg in the leg cut. However, these values were calculated with all associated subcutaneous fat and it is known that many consumers trim on plate, especially the loin cut. Considering the fact that significant differences were apparent between the current study and previous data derived from other countries, it emphasizes the importance of determining the nutrient composition of South African food products in order to increase the validity of the SA food composition tables. Food-based approaches targeting the relief of micronutrient deficiency usually encourage the consumption of animal foods together with the consumption of green leafy vegetables (GLV). The inclusion of GLV and red meat, two micronutrient rich foods, can be a strategy based on mutual supplementation to combat nutritional deficiencies as it has the potential to alleviate numerous micronutrient deficiencies including iron and vitamin A deficiency. / Dissertation (MSc)--University of Pretoria, 2009. / Food Science / unrestricted

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