Furosemide (Lasix®), abbreviated as FR and also known as frusemide, is a drug used for renal problems and treatment of cardiac edema. Various polymorphic forms of furosemide, dependent upon the method of preparation and thermal treatment, have been reported. The main thermal decomposition product of furosemide has been identified as saluamine. The dissolution properties of furosemide have also been reported to be improved by complexation with beta-cyclodextrin. Photostabilities of the different crystal forms have been studied. Differential scanning calorimetry (DSC) and thermogravimetry (TG) have been used to examine the thermal behaviour of furosemide itself and of its physical and kneaded mixtures with betacyclodextrin (BCD) and gamma-cyclodextrin (GCD). There is strong evidence from DSC that complex formation between FR and GCD occurs. This is supported by IR and XRD data. Decreases in the intensity and broadening of the characteristic carbonyl (1660 cm'l) and amine (1588 cm⁻¹) bands in the kneaded mixture, compared to the physical mixture, were observed with IR. X-ray diffraction results for the 1:3 molar ratio FR/GCD kneaded mixture showed a halo diffraction pattern characteristic. of an amorphous solid and did not resemble patterns from the drug, or the gamma, cyclodextrin, or the physical mixture. Photostability studies have been conducted on solid furosemide and its mixtures with GCD or BCD. An HPLC method was developed to determine the amount of drug remaining after exposure and the presence of any degradants. Results indicated that about 10% degradation of the drug occurred during exposure for 16 hours at 550 W/m², with the appearance of polar degradants. Although IR and DSC results for the 1:3 molar ratio FR/GCD kneaded mixture showed a probable strong interaction between FR and GCD, the photostability of FR was decreased. The 1 :3 molar ratio FR/BCD kneaded mixture showed less photo-degradation than the 1:3 molar ratio FR/GCD mixture under similar conditions, suggesting that inclusion of the drug molecule (FR) is different in the two cyclodextrins.

Abstract The aim of the present work was to elucidate the incidence, associated risk factors and natural course of nephrocalcinosis (NC) in very low birth weight (VLBW) infants, and to evaluate renal function in affected infants during early childhood. The occurrence and course of NC in full-term infants receiving furosemide and in infants with congenital lactase deficiency were also studied. A total of 129 VLBW infants were screened for NC by renal ultrasonography (US) at 2 and 6 weeks and 3 months, and ultrasonic follow-up was performed on the infants with NC at 6, 12, 18 and 24 months, and thereafter annually up to age 5-6 years or until ultrasonic resolution. NC was classified according to its pyramidal localisation and extent. Twenty VLBW children with neonatal NC and 20 control pairs without the condition were examined for renal function at 4.7 (SD 1.1) vs. 4.6 (0.9) years of age. Thirty-six full-term infants who had received furosemide treatment for congestive heart failure for at least 4 weeks and 36 control infants without any diuretic therapy were examined by renal US and by means of a random urine sample taken at a median age of 2.9 vs. 3.4 months. The case records of the 11 infants with congenital lactase deficiency were analysed for NC, and these children were re-evaluated at 2 to 10 years of age. NC was detected in 26 out of the 129 VLBW infants (20%). The infants with NC were sicker and smaller than the unaffected ones and had more often received furosemide, dexamethasone and theophylline treatment. NC was peripheral in 14 cases (54%), scattered in 7 (27%) and extensive in 5 (19%). All the casesof peripheral NC showed resolution at 12 months, but abnormal renal findings were seen in 3 out of the 7 with scattered NC and 3 out of the 4 surviving children with extensive NC at 24 months, in 2 of whom the condition persisted at age 5-6 years. The children with neonatal NC showed increased urinary calcium and μ2-microglobulin excretion as compared with the controls in early childhood, but there was no significant difference in distal tubular acidification capacity, nor in estimated creatinine clearance. Five out of the 36 full-term infants receiving long-term furosemide had NC, but none of the controls. The daily dose of furosemide and the urinary calcium concentration were both higher in the infants with NC. Abnormal renal findings were still visible in two of the cases at 24 months of age. Hypercalcaemia was found in 7 out of 10 infants with congenital lactase deficiency tested at the time of diagnosis, and NC was seen in 5 of the 7 cases examined by renal ultrasonography. No constant dysfunction in calcium homeostasis was seen at re-evaluation, but nephrocalcinotic changes were observable in 3 out of the 11 children. NC may complicate not only the course of VLBW infants, but also that of full-term infants with calciuric medication and diseases that involve hypercalcaemia. Some renal tubular dysfunction may result from NC in former preterm infants, but overall kidney function seems not to be seriously compromised in early childhood.

This study was conducted to test the hypothesis that, during renal development, the Na-K-2Cl cotransporter type 2 (NKCC2) activates the tonicity-responsive enhancer binding protein (TonEBP) transcription factor by creating medullary hypertonicity. TonEBP, in turn, drives the expression of aldose reductase (AR) and urea transporter-A (UT-A). Kidneys from 13- to19-day-old fetuses (F13-F19), 1- to 21-day-old pups (P1-P21), and adult mice were examined by immunohistochemistry. NKCC2 was first detected on F14 in differentiating macula densa and thick ascending limb (TAL). TonEBP was first detected on F15 in the medullary collecting duct (MCD) and surrounding endothelial cells. AR was detected in the MCD cells of the renal medulla from F15. UT-A first appeared in the descending thin limb (DTL) on F16 and in the MCD on F18. After birth, NKCC2-positive TALs disappeared gradually from the tip of the renal papilla, becoming completely undetectable in the inner medulla on P21. TonEBP shifted from the cytoplasm to the nucleus in both vascular endothelial cells and MCD cells on P1, and its abundance increased gradually afterward. Immunoreactivity for AR and UT-A in the renal medulla increased markedly after birth. Treatment of neonatal animals with furosemide dramatically reduced expression of TonEBP, AR, and UT-A1. Furosemide also prevented the disappearance of NKCC2-expressing TALs in the papilla. The sequential expression of NKCC2, TonEBP, and its targets AR and UT-A and the reduced expression TonEBP and its targets in response to furosemide treatment support the hypothesis that local hypertonicity produced by the activity of NKCC2 activates TonEBP during development.

The first harmful effect of caffeine on genetic material was discovered in 1948. The next thirty-three years have given way to public concern and even anxiety over chromosome damage caused by caffeine. More recently, the late 1960’s, concern has arisen over the synergistic characteristic of caffeine.Furosemide, also known as Lasix, is a diuretic and is the drug of choice in treating patients with renal disease. Very little research has been done on the harmful effects furosemide may have on genetic material.This study will investigate the mutagenic potential of caffeine and the mutagenic potential of furosemide. It will also investigate the synergistic effect of caffeine when given with furosemide. Both studies will to done with increasing noses of caffeine and with increasing doses of furosemide.Fifty-six 72-hour chromosome cultures will be set up using fourteen different blood specimens. Four cultures will be made peg- specimen. Specimens numbering one to four will be testing the mutagenic potential of caffeine. Specimens numbering five to eight will be testing the mutagenic potential of furosemide. And, Specimens nine to fourteen will be testing the synergistic effect of caffeine with furosemide.Damage will be assessed by the number of chromosome aberrations, either in the form of gaps or breaks, and the degree of pulverization.Ball State UniversityMuncie, IN 47306

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 88-105).

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Agradecemos a compreensão. on 2016-07-15T13:11:51Z (GMT) / Submitted by PABLO COSTA MAGALHÃES null (pablocmagalhaes@hotmail.com) on 2016-08-08T17:25:51Z No. of bitstreams: 1 dissertaão repositório.pdf: 1610442 bytes, checksum: b8a09d1a08e373e71bb20b1f29f2b92e (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-08-09T14:48:38Z (GMT) No. of bitstreams: 1 magalhaes_pc_me_bot.pdf: 1610442 bytes, checksum: b8a09d1a08e373e71bb20b1f29f2b92e (MD5) / Made available in DSpace on 2016-08-09T14:48:38Z (GMT). No. of bitstreams: 1 magalhaes_pc_me_bot.pdf: 1610442 bytes, checksum: b8a09d1a08e373e71bb20b1f29f2b92e (MD5) Previous issue date: 2016-05-23 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A hemorragia pulmonar induzida pelo exercício (HPIE) diminui a performance atlética dos animais e acarreta prejuízos aos criadores. Por apresentar etiologia não elucidada, seu tratamento paliativo é a administração de furosemida, diurético que reduz o volume plasmático, a pressão sanguínea, a ruptura alveolar e a hemorragia. Considerando que a acupuntura atua sobre os diversos sistemas do organismo e levando-se em consideração os efeitos adversos da furosemida, a farmacopuntura poderia promover a diurese e minimizar tais efeitos indesejados. Objetivou-se avaliar o possível efeito dessa técnica em equinos em um projeto piloto. Para tal utilizou-se seis animais, submetidos à quatro tratamentos a um intervalo de pelo menos um dia: furosemida, farmacopuntura associada a acupuntura, falsa farmacopuntura e controle no qual os animais não receberam nenhum tratamento. Avaliou-se o tempo de início da micção após os tratamentos, o débito urinário, a densidade e a frequência de micção. O tempo até o início de micção foi semelhante entre os grupos furosemida e farmacopuntura e se deu nos primeiros 20 minutos de coleta, sendo maior nos demais grupos. O débito urinário foi menor para o grupo controle que o tratado com furosemida. Não houve diferença para a densidade e a micção foi mais frequente após administração de furosemida comparada ao controle e a falsa farmacopuntura. Concluiu-se que a farmacopuntura não influenciou o débito urinário dos animais e, desta forma, optou-se no estudo principal em avaliar apenas o efeito da acupuntura com agulhas secas na prevenção da HPIE. Foram utilizados 18 equinos Puro Sangue Inglês. Cada animal foi seu próprio controle, sendo submetido a exercício intenso três vezes com intervalos de 15 dias, sendo a primeira sem nenhum tratamento (C) e as outras duas, uma após receber 250 mg de furosemida IV (F) e outra após uma sessão de acupuntura (A), ambas quatro horas antes do exercício. Os animais foram avaliados 30 minutos antes, imediatamente após e 30 minutos após o exercício sendo realizada a avaliação clínica dos parâmetros vitais e do sistema respiratório, exame endoscópico do trato respiratório e coleta de sangue para mensuração de volume globular (VG) e proteína total (PT). O grau de sangramento teve mediana igual a 3 no controle, sem diferença estatística (P>0,05) para o tratamento com acupuntura que teve mediana igual a 2,5. O tratamento com furosemida diferiu dos demais (P<0,001) apresentando mediana 0,5 para tal variável. Quanto ao exame clínico dos parâmetros vitais e do sistema respiratório, a maioria das variáveis apresentou diferença estatística entre os momentos pré e pós, independente do tratamento avaliado, sem apresentar, entretanto, diferenças entre os tratamentos em um mesmo momento. O VG médio foi mais elevado para o tratamento com furosemida em relação aos demais nos momentos pré e pós exercício. Os valores obtidos de PT diferiram entre os momentos pré e pós, entretanto sem diferir entre os tratamentos avaliados. Concluímos então que apenas uma sessão de acupuntura aplicada quatro horas antes da realização de exercício em cavalos Puro Sangue Inglês de corrida não é capaz de reduzir o grau de sangramento decorrente da HPIE. Novas avaliações com tratamentos contínuos e prolongados devem ser feitas para se inferir melhor a respeito da eficácia da técnica. / The exercise-induced pulmonary hemorrhage (EIPH) decreases athletic performance of animals and causes loss to owners. As its etiology has not yet been elucidated, the palliative treatment is the administration of furosemide, a diuretic that reduces plasma volume, blood pressure, alveolar rupture and hemorrhage. Whereas acupuncture acts on various body systems and taking into account the adverse effects of furosemide, pharmacopuncture could promote diuresis and minimize these adverse effects. We aimed to evaluate the possible effect of this technique in horses in a pilot project. For this purpose we used six animals that underwent four treatments with an interval of at least one day: furosemide, pharmacopuncture associated with acupuncture, false pharmacopuncture and control when animals didn't receive any treatment. We evaluated the urination start time after treatment, urine output, the density and frequency of urination. The time to onset of urination was similar between the groups furosemide and pharmacopuncture and was given at the first 20 minutes of collection, being higher in other groups. Urine output was lower in the control group than the one treated with furosemide. There was no difference in the density and urination was more frequent after furosemide administration compared to the control and false pharmacopuncture. It was concluded that the pharmacopuncture did not influence the urinary output of animals and, therefore, it was decided in the main study to evaluate only the effect of acupuncture with dry needles in preventing EIPH. For this, 18 Thoroughbred horses were used. Each animal was its own control, being subjected to intense exercise three times with an interval of 15 days, the first without treatment (C) and the other two, one after receiving 250 mg of furosemide IV (F) and the other after an acupuncture session (A) both four hours before exercise. The animals were evaluated 30 minutes before and 30 minutes after exercise. It was performed clinical assessment of vital signs and respiratory system, endoscopic examination of the respiratory tract and blood collection for packed cell volume (PCV) measurement and total plasmatic protein (TP). The degree of bleeding had a median of 3 in control, with no statistical difference (P> 0.05) for the acupuncture treatment that had a median of 2.5. The treatment with furosemide differed from the others (P <0.001) presenting median 0.5 for this variable. For the clinical examination of the vital signs and respiratory system, most of the variables presented statistical difference between pre and post moments, regardless of treatment assessed without differences between treatments at the same moment evaluated. The average PCV was higher for treatment with furosemide compared to other pre and post exercise times. The values obtained from TP differ between pre and post, however without significant differences among the treatments. We concluded that only one acupuncture session applied four hours prior to exercise in racing Thoroughbred horses are not able to reduce the degree of bleeding resulting from EIPH. New assessments with continuous and prolonged treatment should be made to better infer about the effectiveness of the technique. / FAPESP: 2014/14976-2

Orientador: Stelio Pacca Loureiro Luna / Resumo: A hemorragia pulmonar induzida pelo exercício (HPIE) diminui a performance atlética dos animais e acarreta prejuízos aos criadores. Por apresentar etiologia não elucidada, seu tratamento paliativo é a administração de furosemida, diurético que reduz o volume plasmático, a pressão sanguínea, a ruptura alveolar e a hemorragia. Considerando que a acupuntura atua sobre os diversos sistemas do organismo e levando-se em consideração os efeitos adversos da furosemida, a farmacopuntura poderia promover a diurese e minimizar tais efeitos indesejados. Objetivou-se avaliar o possível efeito dessa técnica em equinos em um projeto piloto. Para tal utilizou-se seis animais, submetidos à quatro tratamentos a um intervalo de pelo menos um dia: furosemida, farmacopuntura associada a acupuntura, falsa farmacopuntura e controle no qual os animais não receberam nenhum tratamento. Avaliou-se o tempo de início da micção após os tratamentos, o débito urinário, a densidade e a frequência de micção. O tempo até o início de micção foi semelhante entre os grupos furosemida e farmacopuntura e se deu nos primeiros 20 minutos de coleta, sendo maior nos demais grupos. O débito urinário foi menor para o grupo controle que o tratado com furosemida. Não houve diferença para a densidade e a micção foi mais frequente após administração de furosemida comparada ao controle e a falsa farmacopuntura. Concluiu-se que a farmacopuntura não influenciou o débito urinário dos animais e, desta forma, optou-se no estudo pr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The exercise-induced pulmonary hemorrhage (EIPH) decreases athletic performance of animals and causes loss to owners. As its etiology has not yet been elucidated, the palliative treatment is the administration of furosemide, a diuretic that reduces plasma volume, blood pressure, alveolar rupture and hemorrhage. Whereas acupuncture acts on various body systems and taking into account the adverse effects of furosemide, pharmacopuncture could promote diuresis and minimize these adverse effects. We aimed to evaluate the possible effect of this technique in horses in a pilot project. For this purpose we used six animals that underwent four treatments with an interval of at least one day: furosemide, pharmacopuncture associated with acupuncture, false pharmacopuncture and control when animals didn't receive any treatment. We evaluated the urination start time after treatment, urine output, the density and frequency of urination. The time to onset of urination was similar between the groups furosemide and pharmacopuncture and was given at the first 20 minutes of collection, being higher in other groups. Urine output was lower in the control group than the one treated with furosemide. There was no difference in the density and urination was more frequent after furosemide administration compared to the control and false pharmacopuncture. It was concluded that the pharmacopuncture did not influence the urinary output of animals and, therefore, it was decided in the main study to evalua... (Complete abstract click electronic access below) / Mestre

No description available.

Thoroughbred racehorses undergo strenuous exercise which often leads to the occurrence of exercise-induced pulmonary hemorrhage (EIPH), in which capillaries rupture within the alveoli in the lungs causing bleeding. Severe cases of EIPH lead to epistaxis and may result in fatality. Presently, the loop diuretic furosemide is the only medication approved to mitigate the effects of EIPH. Often regarded in the racing industry as "performance enhancing" due to 4% weight loss ensued by its diuretic effect, it is unknown what effects furosemide may have on muscle recovery. Therefore, the objective of this study was to determine the effects various doses of furosemide may have on equine satellite cell (eqSC) myogenesis and metabolism. Mitotic index was increased (P<0.05) as a result of treatment with 100 µg/mL furosemide, a 10-fold pharmacological dose, in comparison to vehicle, but was not different (P>0.05) compared to the physiological dose of 10 µg/mL furosemide. Average cell number decreased (P<0.05) in the excess furosemide group compared to all other groups. Pax7 expression did not differ (P>0.05) between groups. Expression of the differentiation transcription factor myogenin, and embryonic sarcomeric myosin heavy chain decreased (P<0.05) when cells were treated with 100 µg/mL furosemide. Fusion index and myotube area decreased (P<0.05) as a result of treatment with excess furosemide. Glycogen concentration in myotubes was lower (P<0.05) following treatment with 100 µg/mL furosemide, while IGF-1 was unsuccessful in rescuing the effects of furosemide. Excess furosemide decreased expression of muscle creatine kinase while increasing expression of phosphoglucomutase 1, glycogen synthase 1, and glycogen branching enzyme 1 (P<0.05). Excess furosemide decreased basal oxygen consumption rate (OCR) and increased OCR after addition of oligomycin (P<0.05). Excess furosemide did not affect myotube glycolysis rates in vitro. In conclusion, furosemide inhibits muscle differentiation and oxidative metabolism in eqSCs. / Master of Science / Thoroughbred racehorses often bleed from the lungs as a result of high-intensity exercise. This condition can oftentimes be fatal depending on severity. Furosemide, is used in the industry to reduce blood pressure within the lungs during racing to prevent bleeding. Furosemide, a diuretic given four hours prior to a race, causes a horse to excrete up to 4% of its body weight. This effect of furosemide decreases the weight a horse must carry during a race, thus allowing the horse to run faster. Therefore, deemed as a performance enhancing drug due to its effects on the kidney, to our knowledge, no research has been conducted on what effects furosemide might have on muscle generation. High-intensity exercise causes massive muscle damage and therefore must be repaired to prepare for the next bout of exercise. Muscle generation is called myogenesis. Stem cells, or satellite cells, that lie within the muscle become activated, recognizing the need for muscle repair. Satellite cells divide, increasing in cell number and then fuse together, forming new muscle fibers. Satellite cells undergo different types of metabolism depending on their state of development. For example, proliferating cells require glucose for energy, while cells fusing together forming myotubes, require oxidative metabolism for long-lasting energy. Therefore, the objective of this study was to determine the effects furosemide might have on muscle formation and metabolism. The excess furosemide dose (100 µg/mL) decreased cell proliferation. The expression of regulatory factors responsible for forming myotubes at different stages of muscle development are decreased when cells were treated with the defined excess furosemide dose. Furosemide decreased the ability of satellite cells to generate myotubes. Glycogen concentration was also decreased as a result of excess furosemide treatment. Gene expression of enzymes involved in glycogen synthesis were increased from treatment with our excess furosemide dose. No effect of furosemide was seen on glycolysis, whereas oxidative metabolism suffered as a result of treatment with excess furosemide. In conclusion, furosemide does indeed affect muscle generation and oxidative metabolism.

A avaliação da estabilidade dos medicamentos e sua correta utilização em diferentes veículos de infusão são fundamentais para garantir a manutenção das características terapêuticas do fármaco e para promover minimização de eventos adversos. Incompatibilidades entre as estruturas dos fármacos, em diferentes veículos de administração, podem gerar possíveis associações antagônicas ou sinérgicas, resultando em alterações das propriedades físico-químicas e, consequentemente, dos efeitos farmacológicos e das respostas clínicas esperadas. A proteína verde fluorescente (GFP) por apresentar propriedades de sensibilidade e especificidade, mostra-se promissora como potencial biossensor da estabilidade de fármacos em soluções parenterais de grande volume (SPGV), por apresentar sensibilidade a alterações das propriedades físico-químicas do meio. GFP é uma proteína compacta, globular e ácida, composta de um monômero de 27kDa, que vem sendo extensivamente utilizada como indicador biológico em processos de esterilização e desinfecção devido a sua estabilidade a altas temperaturas. O surgimento de métodos analíticos modernos e de alta precisão como a espectrofotometria de UV e a cromatografia líquida de alta eficiência (HPLC), alinhados a potencial utilização das proteínas fluorescentes como forma de avaliar as alterações da estabilidade de fármacos nas SPGV, vêm contribuir para a correta e racional utilização dos medicamentos no ambiente hospitalar. Diante disso a avaliação da estabilidade do coquetel de fármacos composto por furosemida e aminofilina em solução parenteral de 20% manitol e 0,9% NaCl foi sugerida. Amostras foram preparadas nas seguintes soluções (v/v): 20% manitol ou 0,9% NaCl na seguintes proporções utilizadas frequentemente na prática clínica: (i) 80% solução parenteral adicionada de 16% furosemida e 4% água para injeção (excipiente do fármaco aminofilina), (ii) 80% solução parenteral adicionada de 4% aminofilina e 16% água para injeção + NaOH (excipiente do fármaco furosemida), (iii) 80% solução parenteral, adicionada de 16% furosemida e 4% aminofilina (coquetel). As amostras foram avaliadas em espectrofotômetro imediatamente após o preparo e após um período 20h, em y=228nm e y=275nm para os fármacos furosemida e aminofilina, respectivamente. Para os fármacos individualmente associados às SPGV na faixa de pH 10-11, as concentrações finais obtidas foram correspondente ás inicialmente adicionadas e para o fármaco aminofilina foi estável até o período de 20h. Para avaliar a estabilidade dos fármacos associados à solução de 20% manitol a utilização de HPLC mostrou manutenção da estabilidade dos fármacos durante o período de infusão de até 20h. A proteína GFP adicionada as soluções das amostras na concentração 8?g/mL e determinada em espectrofluorímetro (yex=394nm, yem=509nm), mostrou resultados promissores quanto ao sua potencial utilização como biossensor da estabilidade dos fármacos furosemida e aminofilina nas soluções parenterais, mostrando comportamento de concentração e intensidade de fluorescência característicos e proporcionais a perda da estabilidade das soluções. A utilização de proteínas fluorescentes como potencial biossensor da estabilidade de fármacos em soluções parenterais é importante por fornecer parâmetros que garantam a eficácia dos medicamentos veiculados em soluções parenterais, racionalizando a sua utilização no ambiente hospitalar. / Parenteral solutions (PS) are used as vehicles in drugs administration to the organism. The development of analytical techniques that enables the detection of incompatibilities between drugs and PS is mandatory to guarantee their correct association with minimum adverse events. Incompatibilities of drugs in different infusion vehicles change according to physical-chemical properties of solutions, because of the molecular structure, chemical compounds used for preservation and stability of PS components. This fact can promote antagonic or synergic effects with loss of clinical response. The green fluorescent protein (GFP) is compact, globular, and acidic, with 27KDa and has been used as a biologic indicator of sterilization and disinfection process because it is easily detected using UV light, spectrofluorometry, with high thermal stability. GFP specificity and sensibility to physical-chemical changes in the media favors its use as a biosensor for drugs stability in parenteral solutions. The development of analytical methods such as spectrophotometry and high performance liquid chromatography (HPLC) in association with the fluorescent properties of some proteins enable the detection of potential incompatibilities between drugs and parenteral solutions, promoting a rational utilization of drugs in hospital. The evaluation of a diuretic cocktail with furosemide and aminophylline administrated in parenteral solutions of 20% mannitol and 0.9% NaCl was studied. Samples were prepared either in 20% mannitol or 0.9 % NaCl (PS), as follows: (i) 80% parenteral solution added with 16% furosemide and 4% WFI (solvent for aminophylline), (ii) 80% parenteral solution 4% aminophylline and 16% WFI+NaOH (pH 9-10, solvent for furosemide), (iii) 80% parenteral solution, added with 16% furosemide and 4% aminophylline (cocktail). Samples were diluted and prepared in a pH range of 6.5-7.5 and pH 10-11 for aminophylline and furosemide, individually and associated. The samples were prepared with PS including the excipients used in the drugs formulations. The absorbance was determined immediately after preparation and after 20 hours at 25°C and y= 228 nm, 275 nm, respectively for furosemide and aminophylline. GFP stability was determined in a spectrofluorometer (yex=394nm, yem=509nm) by adding 8 µg/mL of the purified protein in a 3.0mL sample (25°C) and the fluorescence intensity was evaluated after 20 hours. For both drugs in parenteral solutions (pH 10-11) the final concentrations observed were similar to the expected, aminophylline was also stable after 20h. When both drugs were associated in parenteral solutions of 20% mannitol, the use of HPLC showed stability for both drugs in the first 20h. The fluorescence intensity of GFP added to the samples was determined in spectrofluorometer (yex=394nm, yem=509nm), showing that fluorescence intensity was proportional to the drugs stability loss. Therefore, the utilization of fluorescence proteins is important to assure the drugs effectiveness and rational utilization in hospital places.