Redução da taxa de filtração glomerular em pacientes críticos em uso de vancomicina: um estudo transversal / Decrease of the glomerular filtration rate in critically ill patients using vancomycin: a cross-sectional study

Objetivo: o presente trabalho teve como objetivo avaliar os fatores clínicos e medicamentosos relacionados com a redução da Taxa de Filtração Glomerular (TFG) em pacientes críticos em uso de vancomicina. Métodos: trata-se de um estudo transversal em que pacientes em uso de vancomicina, maiores de 18 anos, hospitalizados em terapia intensiva, foram selecionados no período de agosto a dezembro de 2019. Foram excluídos os pacientes que tiveram permanência inferior a 48h na unidade, aqueles com doença renal crônica e/ou que tiveram antimicrobiano suspenso nas primeiras 48h. Os dados clínicos e laboratoriais foram coletados do prontuário nas mesmas datas das coletas de amostras sanguíneas. As amostras de sangue foram coletadas no vale a partir do terceiro dia de tratamento. Os níveis de vancomicina foram medidos usando VANC VITROS ®. Os dados foram analisados através do software R. Resultados: 54 pacientes foram incluídos, sendo 68,5% do sexo masculino, 98,1% em ventilação mecânica, com foco respiratório (51,2%) e isolado Acinetobacter baumanni (38,0%). As concentrações de vancomicina variaram entre 5,0 e 50,0µg/mL, média 21,6 (DP: 10,6) µg/mL; 50% dos pacientes apresentaram concentração acima de 20µg/mL e 66,7% piora da TFG após o tratamento. A concentração de vancomicina foi a única variável diretamente relacionada com o desenvolvimento da alteração na função renal (p=0.0037). Não foi possível estabelecer a influência da comedicação na redução da taxa de filtração glomerular (TFG). Conclusão: as doses usuais de vancomicina ajustadas por meio da função renal não atingiram os níveis séricos terapêuticos recomendados de vancomicina, sendo relacionados à nefrotoxicidade.

Objective: we aimed to evaluate clinical and drug factors related to the Glomerular Filtration Rate (GFR) reduction in critically ill patients using vancomycin. Methods: This is a cross-sectional study where critically ill patients using vancomycin, aged over 18 years, were selected from August to December 2019. Patients were excluded when hospitalized for less than 48 hours in the unit, those with chronic kidney disease, and/or who had their antimicrobial suspended in the first 48 hours. Clinical and laboratory data were collected from the medical record on the same days as the blood sample collection. All blood samples were collected at the trough during the third day of vancomycin treatment. Vancomycin levels were measured using VANC VITROS ®. Data analysis was analyzed by R software. Results: 54 patients were included, 68.5% male, 98.1% mechanical ventilation, respiratory focus (51.2%), and isolation of Acinetobacter baumanni (38.0%). Vancomycin concentrations ranged between 5.0 and 50.0µg/mL, mean of 21.6 (SD: 10.6) µg/mL; 50% of patients with concentrations above 20µg/mL and 66.7% worsened GFR after vancomycin treatment. Vancomycin concentration was the only variable directly related to the development of renal malfunction (p=0.0037). It was not possible to establish the influence of co-medication in the reduction of the glomerular filtration rate (GFR). Conclusion: the usual doses of vancomycin adjusted by renal function did not reach the recommended therapeutic serum levels of vancomycin, being related to nephrotoxicity.

Development of the stability-indicating method, structural elucidation of new photodegradation products from terconazole by LC-MS TOF, and in vitro toxicity.

Terconazole (TCZ) was the first triazole antifungal drug launched in the market and has been used in the treatment of vulvovaginal candidiasis. It is also indicated to treat dermatophytosis and fungal ocular infections. However, some of the degradation products from triazole drugs have been reported to be toxic, justifying the need of further investigations about the stability of TCZ. identification of its degradation products and evaluation of their toxicity considering the new possibilities of therapeutic indications. Therefore, in this work a systematic investigation regarding photostability of TCZ was conducted. The active pharmaceutical ingredient (API) and its methanolic solution (100 µg mL-1) were kept into a photostability chamber under a UV light (200 Wh/m2; 1.2 × 106 lux/h) during 5 days and 90 min, respectively. A high-efficiency liquid chromatography method was developed for separation and identification of TCZ and its degradation products. The solid-state API remained stable throughout the test, whereas an extensive degradation was observed when in solution. In this case, four degradation products not yet reported in the literature were identified and characterized by electrospray ionization high-resolution quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). Two degradation products presented m/z of 498 and the other two of 496 and 464, respectively. The results suggest that the degradation follows a first-order kinetic and involves the loss of chlorine atoms from the 2,4-dichlrophenyl moiety. Finally, TCZ submitted to the same stress condition as the API solution, increased significantly the opacity during the bovine corneal opacity and permeability test method (BCOP) indicating a potential to cause ocular toxicity. Further studies using the pure photolysis degradation products of TCZ characterized in this work are still necessary to confirm this find.

Mupirocin ointments: In vitro x In vivo bioequivalence evaluation

Abstract Bioequivalence (BE) assessment of topical drug products is a long-standing challenge. Agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published several drafts in recent years suggesting different approaches as alternative to evaluate the BE. A proposed Topical Classification System (TCS) has even been discussed. Given the above, the objective of this research was to use in vitro and in vivo BE approaches to evaluate Brazilian marketed mupirocin (MPC) ointments, previously classified as TCS class The in vitro permeation test (IVPT) was performed by applying formulations to pig skin by Franz cells. The in vivo methodology was dermatopharmacokinetic (DPK). These approaches (in vivo tape stripping and IVPT) demonstrated capability of distinguishing among different formulations, thus making them useful methodologies for BE evaluation.

Characterization, in vitro dissolution, and pharmacokinetics of different batches of efavirenz raw materials.

OBJECTIVE: To perform the solid-state characterization and the in vitro-in vivo correlation (IVIVC) of three batches of efavirenz (EFV) active pharmaceutical ingredients. SIGNIFICANCE: EFV is an effective anti-HIV drug. Due to the poor aqueous solubility, the rate and extent of EFV absorption deeply depend on its dissolution characteristics. METHODS: Thermal analyses, x-ray diffraction, and particle size distribution were performed. The saturation solubility and dissolution profiles were assessed in 0.5% (w/v) sodium lauryl sulfate (SLS), fasted-state simulated intestinal fluid (FaSSIF), and fed-state simulated intestinal fluid (FeSSIF) using a flow-through cell. Each batch was orally administered to Wistar rats and the pharmacokinetic parameters were correlated with those obtained from in vitro dissolution. RESULTS: All batches of EFV consisted polymorph I. EFV-A presented the lowest particle size distribution [d(v,0.5) = 197.8 µm; d(v,0.9) = 444.6 µm] followed by EFV-B [d(v,0.5) = 223.9 µm; d(v,0.9) = 481.1 µm], and EFV-C [d(v,0.5) = 240.8 µm; d(v,0.9) = 497.3 µm]. The saturated solubility in FaSSIF was 36% and 40% of that in FeSSIF and SLS, respectively. EFV-A presented the fastest rate and largest extension of dissolution than EFV-B and C (79.15%, 69.93% and 54.22%, respectively, as well as the highest maximum plasma concentration. Levels B, C, and multiple-C of IVIVC models were achieved. CONCLUSION: The FaSSIF medium discriminated the dissolution profiles of EFV APIs. Small differences in particle size distribution had a significant impact on the biopharmaceutical parameters of EFV, suggesting that strict control of such parameter is an important aspect during API development and drug formulation.

Critical analysis on the use of cholecalciferol as a COVID-19 intervention: a narrative review.

BACKGROUND: The World Health Organization has declared that a pandemic situation exists in relation to the disease caused by the new coronavirus, COVID-19. So far, the absence of a vaccine against the new coronavirus has led people worldwide to seek various therapeutic alternatives, including use of cholecalciferol. DESIGN AND SETTING: Narrative review developed by a research group at a public university in Recife (PE), Brazil. METHODS: We searched the literature on the use of cholecalciferol for prevention or treatment of COVID-19, using the MEDLINE and LILACS databases, with the keywords "vitamin D", "cholecalciferol", "SARS-CoV-2", "COVID-19" and "coronavirus", from January 1, 2020, to June 10, 2020. Narrative reviews, cohort studies and ecological studies were selected. RESULTS: We retrieved 32 references, of which 8 were considered eligible for intensive review and critical analysis. These comprised five narrative reviews, two observational studies and one protocol proposal. Most of the studies selected reported positive effects from use of vitamin D for prevention or treatment of COVID-19. However, there was little quantitative data to assess the real impact of using this vitamin as an intervention against this disease. CONCLUSIONS: Current studies on vitamin D used for purposes other than bone health promotion cannot be taken as support to justify its use in a disease as recent as COVID-19. Studies of greater robustness, with higher levels of clinical evidence, need to be conducted. Rational use of this vitamin needs to be ensured, thereby minimizing the impacts on the patient and the public healthcare system.

Critical analysis on the use of cholecalciferol as a COVID-19 intervention: a narrative review

ABSTRACT BACKGROUND: The World Health Organization has declared that a pandemic situation exists in relation to the disease caused by the new coronavirus, COVID-19. So far, the absence of a vaccine against the new coronavirus has led people worldwide to seek various therapeutic alternatives, including use of cholecalciferol. DESIGN AND SETTING: Narrative review developed by a research group at a public university in Recife (PE), Brazil. METHODS: We searched the literature on the use of cholecalciferol for prevention or treatment of COVID-19, using the MEDLINE and LILACS databases, with the keywords "vitamin D", "cholecalciferol", "SARS-CoV-2", "COVID-19" and "coronavirus", from January 1, 2020, to June 10, 2020. Narrative reviews, cohort studies and ecological studies were selected. RESULTS: We retrieved 32 references, of which 8 were considered eligible for intensive review and critical analysis. These comprised five narrative reviews, two observational studies and one protocol proposal. Most of the studies selected reported positive effects from use of vitamin D for prevention or treatment of COVID-19. However, there was little quantitative data to assess the real impact of using this vitamin as an intervention against this disease. CONCLUSIONS: Current studies on vitamin D used for purposes other than bone health promotion cannot be taken as support to justify its use in a disease as recent as COVID-19. Studies of greater robustness, with higher levels of clinical evidence, need to be conducted. Rational use of this vitamin needs to be ensured, thereby minimizing the impacts on the patient and the public healthcare system.

A proposed eye ex vivo permeation approach to evaluate pesticides: Case dimethoate.

This study aims to propose different ex vivo methodologies for pesticide evaluation when in contact with ocular mucosa. The first ex vivo study was performed using vertical Franz cells with fresh and refrigerated excised bovine corneas. The second evaluated the permeation through the cornea by using fresh, refrigerated and damaged whole bovine eyes. Both experiments were evaluated by applying 50 µl (of 5 mg/ml solution) of an emulsifiable pesticide formulation (Dimetoato 500 EC®). In the first study, dimethoate profiles and permeation fluxes showed no statistical differences (p < .05) between fresh and refrigerated excised corneas, probably due to the excision procedure generating damage to the cornea by altering stromal structure, irrespective of the refrigeration procedure. In relation to the results obtained for developed ex vivo permeation method in whole eyes, there was a statistical difference (p < .05) between experiments performed with fresh eyes and those performed with refrigerated/damaged eyes. Damage generated by both the refrigeration process and exposure to irritant products led to a five-fold reduction in the amount of corneal-permeated pesticide as well as a two-fold increase in retention. Thus, the ex vivo permeation approach with whole eyes seems to be a simple and reproducible method to evaluate pesticides. It is evident that further evaluations need to be performed using other pesticides with distinct physicochemical characteristics.

Ethephon and fosetyl residues in fruits from São Francisco Valley, Brazil.

This survey describes the occurrence of Ethephon (ETH) and Fosetyl in fruits intended for export produced in the São Francisco Valley, Brazil. The determination of these compounds was carried out by the QuPPe-method (Quick Polar Pesticides Method), which was optimised and successfully validated according to the SANTE/11813/2017. From January 2016 to December 2018 a total of 1048 samples were analysed for ETH residues. In 547 (53%) of the samples, residues below the EU MRL of 1 mg kg-1 were present. In 17 samples (2%) ETH residues were above 1 mg kg-1. Overall, the mean ETH level decreased after 2016. Analyses of fosetyl showed that (18%) of 109 mango samples were positive for this compound. Phosphonic acid was found in concentrations ranging from 0.12 to 3.2 mg kg-1 and 5% of the measurements were above the EU MRL of 2 mg kg-1. The results emphasise the quality control of fruits produced in this region.

Metronidazole thermogel improves retention and decreases permeation through the skin

ABSTRACT Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex(r) (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex(r). Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex(r), but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex(r), when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex(r) for the topical application of MTZ with improved efficacy and reduced side effects.

Acompanhamento farmacoterapêutico em pacientes com dislipidemia em uso de sinvastatina no componente especializado de assistência farmacêutica: um estudo piloto / Pharmacotherapeutic monitoring of simvastatin-treated patients with dyslipidemia in the specialized component of pharmaceutical care: a pilot study

As doenças do aparelho circulatório estão entre as principais causas de morte no mundo. Apesar das recomendações de acompanhamento e avaliação farmacoterapêutica, ainda são desenvolvidos no Brasil poucos estudos científicos, especialmente no componente especializado de assistência farmacêutica. Este estudo teve como objetivo avaliar a influência do serviço-piloto de monitoramento farmacoterapêutico em 14 pacientes idosos com dislipidemia em uso de sinvastatina. O estudo foi realizado na Farmácia de Pernambuco durante um período de seis meses onde se utilizou a metodologia denominada Pharmacist?s Workup of Drug Therapy. O grupo apresentou média de idade 63,3±3,1 anos, com renda familiar e escolaridade baixa, com prevalência de 10 mulheres (71,4%). Além disso, os idosos apresentaram uma média de 5,1±0,8 doenças crônicas, com um consumo de 8,8±2,2 fármacos por idoso. Durante o estudo foram identificados 45 problemas farmacoterapêuticos, cuja média foi de 3,2±1,6 problemas por indivíduo. Dentre os problemas, os associados à segurança da terapia foram os mais frequentes (35,6%), sendo a administração incorreta a causa mais frequente (31,25%). As intervenções farmacêuticas resolveram 37 (82,2%) dos problemas encontrados, reduzindo significativamente os níveis de lipoproteínas aterogênicas, bem como a pressão arterial (p<0,001). Deste modo, o serviço farmacêutico pode ter influenciado nos resultados clínicos destes idosos

Circulatory diseases are among the major causes of death worldwide. Despite the fact that pharmacotherapy assessment and follow-up are strongly recommended, few scientific studies have yet been conducted in Brazil, particularly in the specialized component of pharmaceutical care. The aim of this study was to evaluate the influence of a pilot service of pharmacotherapy follow-up on the condition of 14 elderly patients with dyslipidemia treated with simvastatin. The study was conducted in the Pharmacy of Pernambuco during a 6-month period, employing the Pharmacist?s Workup of Drug Therapy methodology. The group had a mean age of 63.3 ± 3.1 years, with low family income and education levels, 10 of them (71.4%) being women. On average, the patients presented with 5.1 ± 0.8 chronic diseases and consumed 8.8 ± 2.2 drugs each. During the study, 45 pharmacotherapy problems were identified, with a mean of 3.2 ± 1.6 problems per user. Among these problems, those related to therapy safety were the most frequent (35.6%), incorrect administration being the most frequent cause (31.25%). Pharmaceutical interventions solved 37 (82.2%) of the problems encountered, significantly reducing levels of atherogenic lipoproteins and blood pressure (p<0.001). Thus, the pharmaceutical service may have influenced positively the clinical outcomes of these elderly patients

Determination of the critical hydrophile-lipophile balance of licuri oil from Syagrus coronata: application for topical emulsions and evaluation of its hydrating function

The aims of this study were to determine the critical hydrophile-lipophile balance (HLB) of licuri oil, and to perform a clinical assay to evaluate its hydrating effects. For the determination of the HLB, serial emulsions were prepared with the oil. Regarding the clinical study, 13 human subjects were recruited to evaluate the hydrating power of the emulsified preparation containing licuri oil, and comparing it with the same preparation containing sweet almond oil (SAO). The critical HLB of licuri oil was represented by the zones within the concentrations of 10% for the oil and 15% for the pair of tensoactive agents, with a value of 11.8. Both preparations showed similar hydrating power. We propose that licuri oil can be considered a new lipophilic adjuvant with hydrating characteristics, which can be used in cosmetic preparations, replacing consecrated oils, such as SAO.

O objetivo deste estudo foi determinar o EHL crítico do óleo licuri e realizar um ensaio clínico para avaliar os seus efeitos hidratantes. Para a determinação do EHL foram preparadas emulsões seriadas contendo esse óleo. Em relação ao estudo clínico, avaliamos o poder hidratante de preparação emulsionada com óleo de licuri, comparando-a com a mesma preparação contendo óleo de amêndoas doces (OAD), em 13 voluntários. O EHL crítico do óleo de licuri foi representado pelas zonas dentro das concentrações de 10% para o óleo e 15% para o par de tensoativos, com um valor de 11,8 e ambas as preparações mostraram poder hidratante similar. Desta forma, o óleo de licuri pode ser considerado um novo adjuvante lipofílico com função hidratante, o qual pode ser usado em preparações cosméticas, substituindo óleos de consagrado uso, tais como o OAD.

Assay and physicochemical characterization of the antiparasitic albendazole

The aim of this study was to characterize three batches of albendazole by pharmacopeial and complementary analytical techniques in order to establish more detailed specifications for the development of pharmaceutical forms. The ABZ01, ABZ02, and ABZ03 batches had melting points of 208 ºC, 208 ºC, and 209 ºC, respectively. X-ray diffraction revealed that all three batches showed crystalline behavior and the absence of polymorphism. Scanning electron microscopy showed that all the samples were crystals of different sizes with a strong tendency to aggregate. The samples were insoluble in water (5.07, 4.27, and 4.52 mg mL-1, respectively) and very slightly soluble in 0.1 M HCl (55.10, 56.90, and 61.70 mg mL-1, respectively) and additionally showed purities within the range specified by the Brazilian Pharmacopoeia 5th edition (F. Bras. V; 98% to 102%). The pharmacopeial assay method was not reproducible and some changes were necessary. The method was validated and showed to be selective, specific, linear, robust, precise, and accurate. From this characterization, we concluded that pharmacopeial techniques alone are not able to detect subtle differences in active pharmaceutical ingredients; therefore, the use of other complementary techniques is required to ensure strict quality control in the pharmaceutical industry.

O objetivo do trabalho foi caracterizar três lotes de albendazol com técnicas analíticas farmacopéicas e complementares a fim de estabelecer especificações mais detalhadas para o desenvolvimento de formas farmacêuticas. Os lotes ABZ01, ABZ02 e ABZ03 apresentaram fusão em 208 ºC, 208 ºC e 209 ºC. Foi possível evidenciar, por difração de raios X, que os três lotes apresentaram comportamento cristalino e ausência de polimorfismo. Através da microscopia eletrônica de varredura verificou-se que todas as amostras apresentaram cristais com diferentes tamanhos e forte tendência de agregação. As amostras foram insolúveis em água (5,07; 4,27 e 4,52 µg mL-1) e muito pouco solúveis em HCl 0,1M (55,10; 56,90 e 61,70 µg mL-1) e, ainda, apresentaram pureza dentro da faixa especificada pela F.Bras.V (98% a 102%). O método farmacopéico de doseamento não foi reprodutível, e algumas mudanças foram necessárias. O método foi validado e demonstrou ser seletivo, específico, linear, robusto, preciso e exato. A partir dessa caracterização, pode-se concluir que apenas técnicas farmacopéicas não são capazes de detectar diferenças sutis entre os ingredientes farmacêuticos ativos, necessitando, portanto, de uso de outras técnicas complementares para garantir um rígido controle de qualidade na indústria farmacêutica.

Desenvolvimento e validação de método analítico em CLAE-UV para a quantificação de ácido retinóico em microcápsulas de alginato e quitosana / Development and validation of analytical method on HPLC-UV for quantification of retinoic acid in microcapsules of alginate and chitosan

O ácido retinóico (AR) tem sido utilizado para o tratamento de acne severa, rugas, estrias e celulite, no entanto, provoca irritação na pele e sofre rápida degradação quando exposto à luz e ao calor. Métodos analíticos rápidos para quantificação do AR são, portanto, necessários para ensaios de cinética de liberação in vitro. Nesse contexto, o objetivo deste trabalho foi desenvolver e validar um método rápido e sensível para o doseamento do AR em microcápsulas de alginato/quitosana contendo óleo de babaçu dispersas em gel natrosol® por cromatografia líquida de alta eficiência associada à espectroscopia UV e aplicá-lo na avaliação do perfil de liberação in vitro dessas formulações. As análises foram realizadas em modo isocrático utilizando coluna C18 de fase reversa 150 x 4,6 mm (5 μm) com detecção a 350 nm. A fase móvel foi constituída de metanol e ácido acético 1 por cento (85:15 v/v) com vazão de 1,8 mL/minuto. A faixa de linearidade do método foi de 0,5 a 60 μg/mL (r² = 0,999). O método validado mostrou-se sensível, específico, exato, preciso, de baixo custo e o tempo de retenção do AR foi de 5,8 ± 0,4 minutos sendo, desta forma, mais rápido do que os relatados na literatura.

Retinoic acid (RA) has been used in the treatment of severe acne, wrinkles and cellulite. However, it induces skin irritation and rapidly suffers degradation under light and high temperate exposure. Rapid analytical methods to quantify retinoic acid are therefore mandatory for in vitro drug release studies. In this framework, the aim of this study was to develop and validate a rapid and responsive method to quantify the RA in microcapsules of chitosan and alginate containing babassu oil dispersed in natrosol® hydrogel using high performance liquid chromatography (HPLC). Furthermore this method was used to quantify in vitro release kinetics of RA from microcapsules. The analyses have been carried through an isocratic HPLC-UV method using a reversed phase 150 x 4.6 mm C18 (5μm) column, a mobile phase constituted of methanol and 1 percent acetic acid (85:15) at a flow rate of 1.8 mL/min and detection at 350 nm. The linearity range was 0.5-60 μg/mL (r² = 0.999). The validated HPLC-UV method was responsive, specific, accurate, precise, and economic and the RA retention time was 5.8 ± 0.4 minutes, being therefore, faster than that previously reported.

Determination of indinavir in human plasma and its use in pharmacokinetic study

We report the development and validation of a new sensitive, accurate and precise HPLC method with ultraviolet detection for the determination of indinavir sulfate (IND) in human plasma and its application to a bioequivalence study of a new generic formulation. The extraction of IND from plasma samples was achieved by using liquid-liquid extraction with a mean recovery of 73.9 percent. The lower limit of quantification was 0.05 µg/mL. Bioequivalence between the products was determined by calculating 90 percent confidence intervals (CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for the test and reference products, within the 0.80-1.25 interval proposed by ANVISA and FDA. Therefore the medications are bioequivalent and inter-exchangeable.

Foi desenvolvido e validado um novo método, sensível, exato e preciso por Cromatografia a Líquido de Alta Eficiência com detecção em UV para a determinação do sulfato de indinavir (IND) em plasma humano. O fármaco foi extraído do plasma através de extração líquido-líquido obtendo recuperação média de 73.9 por cento, com limite inferior de quantificação de 0.05 µg/mL. O método foi aplicado em estudo de farmacocinética para verificar a bioequivalência entre um novo medicamento genérico e seu produto de referência. A bioequivalência entre os produtos foi determinada calculando-se um intervalo de confiança (IC) de 90 por cento para a razão das médias do produto teste e referência compreendidas entre o intervalo de 0.80-1.25 proposto pela ANVISA e O FDA. Os produtos estudados são bioequivalentes e, portanto, intercambiáveis.

Development and validation of a new method for the quantification of norfloxacin by HPLC-UV and its application to a comparative pharmacokinetic study in human volunteers

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of norfloxacin (NFX) in human plasma and its application to a bioequivalence study between two norfloxacin formulations is described. NFX and the internal standard (cyprofloxacin) were extracted from plasma using liquid-liquid extraction. Chromatographic separation of norfloxacin, cyprofloxacin and plasma interferents was achieved with a C-18 column and a mobile phase consisting of 20 mM sodium hydrogen phosphate buffer pH 3.0 and acetonitrile (88:12, v/v) and quantitation was done at 280 nm. The method was linear from 25 to 3000 ng mL-1 (r² > 0.997578), and norfloxacin and cyprofloxacin had an average recovery from plasma of 93.9 percent and 91.2 percent respectively. The RSD of inter-day quality control samples at the lower limit of quantification was less than 15 percent. After a single oral dose (400 mg) of norfloxacin administered to healthy human volunteers using a randomized 2x2 crossover design, pharmacokinetic parameters (AUC0-t, AUC0-00, Cmax, t1/2) were derived from the plasma concentration curves for both formulations. Pharmacokinetic analysis of the data showed that the two formulations were bioequivalent, while no adverse reactions to the drug were observed.

O desenvolvimento e validação de um método simples e preciso por CLAE-UV para quantificação de norfloxacino (NFX) em plasma humano e a sua aplicação a um estudo de bioequivalência entre duas formulações são descritos. NFX e o padrão interno (ciprofloxacino, PI) foram extraídos do plasma através de extração líquido-líquido. A separação cromatográfica do NFX, do PI e dos interferentes do plasma foi realizada com uma coluna C-18 e fase móvel composta de tampão fosfato de sódio 20 mM pH 3,0 e acetonitrila (88/12, v/v) e quantificado em 280 nm. A resposta do detector aos analitos mostrou-se linear entre 25 a 3000 ng mL-1 (r² > 0,997578) e a recuperação média de NFX e PI foi de 93,9 por cento e 91,2 por cento respectivamente. O desvio padrão relativo de amostras analisadas ao nível do limite inferior de quantificação foi menor que 15 por cento. Foi administrada uma dose de NFX (400 mg) por via oral a voluntários humanos em um estudo aberto, aleatório e cruzado 2x2 entre duas formulações. Os parâmetros farmacocinéticos (AUC0-t, AUC0-00, Cmáx, T1/2) foram observados a partir da curva de concentração versus tempo. A análise farmacocinética mostrou que as duas formulações são bioequivalentes entre si. Nenhum efeito adverso foi observado.

Obtenção e avaliação clínica de dentifrícios à base do extrato hidroalcoólico da Lippia sidoides Cham (Verbenaceae) sobre o biofilme dentário / Obtention and evaluation of odontologic products made with the crude extract of Lippia sidoides Cham (Verbenaceae) over the dental biofilm

Resumo: Este estudo teve por objetivo obter e avaliar os efeitos de preparações odontológica,creme dental e colutório, à base do extrato hidroalcoólico de Lippia sidoides Cham como coadjuvanteda higiene bucal no controle do biofilme dentário em voluntários humanos. Foram selecionados84 indivíduos, divididos em 4 grupos de 21 elementos, os grupos teste 2 e 3 e os grupos controle1 e 4, avaliados nos tempos 0, 7, 15, 21 e 28 dias. Os resultados demonstraram que o creme dental e o colutório, à base do extrato de Lippia sidoides Cham (grupos 2 e 3 respectivamente), após umperíodo de 28 dias, foram superiores aos produtos utilizados como controle (creme dental de usodiário no grupo 1 e solução de cloreto de cetilpiridíneo no grupo 4), mostrando serem eficientes como coadjuvante no controle do biofilme dentário, pois reduziram de forma estatisticamente significativa o índice de biofilme dentário

This work describes the attainment of odontologic preparations from the crude extract of Lippia sidoides Cham (Verbenaceae) and the evaluation of their effects as an oral hygienic agent in the dental bacterial control on human volunteers. The volunteers (84) were divided into four groups of 21 where test groups are 2 and 3 and control groups are 1 and 4, tested after time periods of 0, 7, 14, 21 and 28 days. The results suggested that the toothpaste and the mouthwash made with the crude extract of Lippia sidoides Cham (Verbenaceae) after a 28 day period were statistically efficient in reducing the dental biofilm caused by bacteria

Desenvolvimento preliminar de gel de lapachol: estudo de permeação in vitro / Preliminary development of lapachol gel: in vitro permeation study

O objetivo do presente estudo foi desenvolver formulações geleificadas do lapachol, substância de conhecida atividade antiinflamatória. Para otimização das formulações, foi verificada a influência da resina de Carbopol® empregada (934P, 940 e 941), do pH da formulação (5, 7 e 8), da concentração do princípio ativo (0,2 por cento, 0,5 por cento e 1,0 por cento) bem como da incorporação de um promotor de absorção (Polissorbato 80) na liberação in vitro do lapachol utilizando células de difusão tipo Franz. Para tanto foram usadas como barreiras membrana sintética Durapore e pele de rato albino tipo Wistar. Os resultados demonstraram que a adição do Polissorbato 80 na formulação promoveu aumento significativo na permeação do princípio ativo através da pele estudada, exceto para os géis contendo 0,2 por cento de lapachol utilizando Carbopol® 934P como agente geleificante...

Tratamento não cirúrgico da bolsa periodontal: estudo comparativo entre a utilização tópica dos géis de tetraciclina e clorexidina / Non surgical periodontal pocket treatment: comparative study between teh topical administration of tetracycline and clorexidine gel

Este trablaho refere-se ao estudo da eficácia da aplicação tópica dos géis de tetraciclina a 15 por cento e clorexidina a 0,12 por cento, ambos usados em associação aos procedimentos básicos, no tratamento da periodontite do adulto. Durante 30 dias, 2 vezes por semana, 14 voluntários, com bolsas periodontais de profundidade 4mm e equivalentes nos hemiarcos superiores e inferiores, receberam raspagem supra e subgengival, profilaxia profissional, instrução de higiene oral e aplicações subgengivais de gel de tetraciclina a 15 por cento e de gel de clorexidina a 0,12 por cento, um tipo de antimicrobiano para cada hemiarco, sendo a escolha feita aleatoriamente. Os molares não foram inclusos na avaliação. Como parâmetros clínicos foram utilizados a profundidade da bolsa (P.B.) e o sangramento à sondagem (S.S.), ambos avaliados quinzenalmente por 5 vezes. após 60 dias desde o início do estudo, a análise estatística evidenciou redução de P.B. em 1,7mm para a tetraciclina e 1,9mm para a clorexidina. Os dois tipos de antimicrobianos também demosntraram grande efetividade em relação à redução de S.S., não havendo diferenças estatísticas significantes. Conclui-se que os agentes antimicrobianos liberados localmente e associados aos procedimentos básicos podem ser usados como alternativa para o tratamento da periodontite do adulto

Isotretinoína e seus efeitos clínicos tóxicos / Isotretinoin-toxicologic clinical studies

A isotretinoína (ácido 13-cis-retinóico) é um derivado da vitamina A (retinol) bastante utilizada, por via oral, no tratamento da acne nódulo-cística grave. Estudos toxicológicos revelaram que ao longo dos quase vinte anos de utilização deste fármaco, no tratamento da acne, surgiram inúmeros efeitos adversos, alguns dos quais já estão comprovados, como o efeito teratogênico e outros, que ainda estão em fase de pesquisa, como a indução da depressão. Neste estudo, serão relatados alguns dos mais importantes e recentes casos de efeitos colaterais induzidos pela isotretinoína, observando-se o risco-benefício no uso deste fármaco