Identification of Asiaticoside from Centella erecta (Apiaceae) as Potential Apyrase Inhibitor by UF-UHPLC-MS and Its In Vivo Antischistosomal Activity.

Schistosomiasis, caused by parasites of the genus Schistosoma, is a neglected disease with high global prevalence, affecting more than 240 million people in several countries. Praziquantel (PZQ) is the only drug currently available for the treatment. S. mansoni NTPDases (known as SmNTPDases, ATP diphosphohydrolases or ecto-apyrases) are potential drug targets for the discovery of new antischistosomal drugs. In this study, we screen NTPDases inhibitors from Centella erecta (Apiaceae) using an ultrafiltration combined UHPLC-QTOF-MS method and potato apyrase, identifying asiaticoside as one of the apyrase-binding compounds. After isolation of asiaticoside from C. erecta extract, we assessed its in vivo antischistosomal activities against Schistosoma mansoni worms and its in vitro enzymatic apyrase inhibition. Also, molecular docking analysis of asiaticoside against potato apyrase, S. mansoni NTPDases 1 and 2 were performed. Asiaticoside showed a significant in vitro apyrase inhibition and molecular docking studies corroborate with its possible actions in potato apyrase and S. mansoni NTPDases. In mice harboring a patent S. mansoni infection, a single oral dose of asiaticoside (400 mg/kg. p.o.) showed significantly in vivo antischistosomal efficacy, markedly decreasing the total worm load and egg burden, giving support for further exploration of apyrase inhibitors as antischistosomal agents.

Simultaneous Monitoring of Azathioprine Metabolites in Erythrocytes of Crohn's Disease Patients by HPLC-UV.

The conversion of azathioprine (AZA) to active 6-thioguanine nucleotides (6-TGN) is essential for its clinical efficacy; however, another metabolite formed, 6-methylmercaptopurine (6-MMP), is related to hepatotoxicity. Blood samples were collected from 37 patients under AZA's treatment, and a new HPLC-UV method was validated and applied for simultaneous quantification of 6-TGN and 6-MMP in erythrocytes of Crohn's disease (CD) patients. The concentration of 6-TGN and 6-MMP found ranged from 4.5 to 2,456 ρmol/8 × 108 red blood cells (RBCs) for 6-TGN and from 170 to 53,951 ρmol/8 × 108 RBCs for 6-MMP. Reduced levels of 6-MMP in patients into combo therapy with AZA and allopurinol (2,031 ρmol/8 × 108 RBCs) have been observed when compared to patients undergoing monotherapy with AZA (9,098 ρmol/8 × 108 RBCs). Additionally, there was a negative correlation (r = -83.7%, P < 0.05) between lymphocyte count and 6-TGN levels. The method developed is reliable, accurate and reproducible and can be used as an important tool in the monitoring routine of patients with CD under AZA treatment, allowing the individualization of the dose, monitoring adherence to the treatment and the evaluation of the clinical outcome of these patients.

Evaluation of copaiba oil as enhancer of ibuprofen skin permeation

Abstract The administration of medications on the skin through transcutaneous routes is a practice that has been used by mankind for millennia. Some studies have been reporting the use of terpenes and natural oils rich in terpenes as an enhancer of cutaneous penetration. Copaiba oil, due to its rich content of terpenes, presents itself as a great choice of penetration enhancer for drugs administered on the skin. In this study, we developed two cream formulations containing 5% of ibuprofen (IBU) and copaiba oil: IBCO5 and IBCO10 with 5% and 10% of copaiba oil respectively. Ex vivo cutaneous penetration/permeation studies of IBU were performed using pig ear skin as biological membrane in the Franz-type diffusion cells. The steady-state flux of IBU samples, IBCO5 (35.72 ± 6.35) and IBCO10 (29.78 ± 2.41) were significantly higher when compared with control without copaiba oil (10.32 ±1.52) and with a commercial product (14.44 ± 2.39). In the penetration analysis, the amount of IBU found in the samples IBCO5 and IBCO10 was markedly higher in the dermis than epidermis. Our results showed that copaiba oil possesses attracting properties in promoting skin penetration and permeation of IBU when added into cream formulations.

Development and validation of a UHPLC-ESI-MS/MS method for the quantification of artepillin C in Brazilian green propolis

Objectives: The aim of this study was the development and validation of a fast method to quantify artepillin C in green propolis using ultra high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS). Methods: High purity (97.8%) artepillin C was isolated from green propolis using chromatography techniques. Quantification was performed using a C18 (2.1 x 100 mm; 1.7 µm) column, gradient of water and methanol (with 0.01% formic acid) as mobile phase, at a flow rate of 0.4 mL/min and 45 ºC in temperature. A mass spectrometer operated in selected reaction monitoring mode to monitor the deprotonated molecular ion of artepillin C (m/z 299) > fragment ion (m/z 200.12). Several parameters such as specificity, linearity, limit of detection (LOD), limit of quantitation (LOQ), precision, accuracy, and robustness were determined. Results: The method was linear in the 50 ­ 400 µg/mL range (r2 = 0.9906), showing LOD = 10.79 µg/mL and LOQ = 32.70 µg/mL with satisfactory intra-day and inter-day precision with relative standard deviation (RSD %) of 1.9% and 3.4%, respectively. The accuracy showed recovery of 93-104%, the method was robust and artepillin C was quantified in green propolis at 6.51%. Conclusions: The proposed method showed advantages in comparison with other methods, such as short analysis time and high selectivity for artepillin C.

Nebulization of Vancomycin Provides Higher Lung Tissue Concentrations than Intravenous Administration in Ventilated Female Piglets with Healthy Lungs.

BACKGROUND: Intravenous vancomycin is used to treat ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus, but achieves high rates of failure. Vancomycin nebulization may be efficient to provide high vancomycin lung tissue concentrations. The aim of this study was to compare lung tissue and serum concentrations of vancomycin administered intravenously and by aerosol in mechanically ventilated and anesthetized healthy piglets. METHODS: Twelve female piglets received a single intravenous dose of vancomycin (15 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of administration. Twelve piglets received a single nebulized dose of vancomycin (37.5 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of the aerosol administration. In each group, vancomycin lung tissue concentrations were assessed on postmortem lung specimens using high-performance liquid chromatography. Blood samples were collected for serum vancomycin concentration measurement 30 min and 1, 2, 4, 6, 8, and 12 h after the end of vancomycin administration. Pharmacokinetics was analyzed by nonlinear mixed effect modeling. RESULTS: One hour after vancomycin administration, lung tissue concentrations in the aerosol group were 13 times the concentrations in the intravenous group (median and interquartile range: 161 [71, 301] µg/g versus 12 [4, 42] µg/g; P < 0.0001). Twelve hours after vancomycin administration, lung tissue concentrations in the aerosol group were 63 (23, 119) µg/g and 0 (0, 19) µg/g in the intravenous group (P < 0.0001). A two-compartment weight-scaled allometric model with first-order absorption and elimination best fit serum pharmacokinetics after both routes of administration. Area under the time-concentration curve from 0 to 12 h was lower in the aerosol group in comparison to the intravenous group (56 [8, 70] mg · h · l vs. 121 [103, 149] mg · h · l, P = 0.002). Using a population model, vancomycin bioavailability was 13% (95% CI, 6 to 69; coefficient of variation = 85%) and absorption rate was slow (absorption half life = 0.3 h). CONCLUSIONS: Administration of vancomycin by nebulization resulted in higher lung tissue concentrations than the intravenous route.

Pharmacokinetic profile and oral bioavailability of Kaurenoic acid from Copaifera spp. in rats.

Kaurenoic acid (KA) is a kaurane diterpene found in several medicinal plants that displays biological activities, such as anti-inflammatory, smooth muscle relaxant and hypotensive response. However, there are no pharmacokinetic data available about this molecule. The purpose of the study was to determine the pharmacokinetic profile and the oral bioavailability of KA in rats. Wistar rats submitted to jugular vein cannulation received 50 mg/kg of KA by intravenous or oral route. The implanted cannula allowed intravenous administration and serial blood collection along 10 h. Analytical quantification was performed by reversed phase HPLC-UV and mobile phase composed by acetonitrile:acidified water (70:30 v/v). The validated analytical method showed precision, accuracy, robustness, reliability and linearity between 0.75 and 100 µg/mL. KA administered intravenously showed a linear and two-compartment kinetic behavior at the tested dose. The following pharmacokinetic parameters were determined: Cmax = 22.17 ±â€¯1.65 mg/L; V = 14.53 ±â€¯1.47 L/kg; CL = 17.67 ±â€¯1.50 mL/min/kg; AUC0-∞ = 2859.65 ±â€¯278.42 mg·min/L, K = 0.073 ±â€¯0.005 h-1 and t1/2ß = 9.52 ±â€¯0.61 h. Oral treatment did not provide detectable plasma levels of KA, avoiding the determination of its bioavailability.

Envolvimento do tabagismo e apoptose na patogênese da doença pulmonar obstrutiva crônica / Involvement of smoking and apoptosis in the pathogenesisof chronic obstructive pulmonary disease

A doença pulmonar obstrutiva crônica (DPOC) é caracterizada pela inflamação crônica das vias aéreas e destruição progressiva do parênquima pulmonar. Esse processo tem como principal fator desencadeante e perpetuante o uso do tabaco. Após a deflagração do início da doença, diversos mecanismos estão envolvidos no seu desenvolvimento; i.e, células inflamatórias nos pulmões (conduzindo à inflamação das vias aérea), desequilíbrio protease/antiprotease (resultando na destruição do parênquima pulmonar) e elevação do estresse oxidativo. É crescente o número de estudos sugerindo que a apoptose celular tem papel crucial na patogênese da DPOC. Este artigo objetiva revisar o envolvimento do tabagismo e da apoptose na patogênese da DPOC e suas interações com outros fatores que a determinam. Os pacientes com DPOC, mesmo após cessar o tabagismo, continuam a desenvolver ciclo de inflamação com níveis elevados de apoptose, o que parece conduzir ao declínio da função pulmonar e muscular periférica. A compreensão desses mecanismos pode ser um caminho para traçar novas estratégias terapêuticas para o manejo da DPOC.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and progressive destruction of lung parenchyma. The main triggering and perpetuating factor of this process is the use of tobacco. After the outbreak of the beginning of the disease, several mechanisms are involved in its development, eg. inflammatory cells in the lungs (leading to inflammation of the airways), protease/antiprotease imbalance (resulting in the destruction of lung parenchyma) and oxidative stress increase. A growing number of studies suggests that cellular apoptosis plays a crucial role in the pathogenesis of COPD. This paper aims at reviewing the involvement of smoking and apoptosis in the pathogenesis of COPD, besides its interactions with other factors that determine it. Patients with COPD, even after quitting smoking, continue to develop cycle of inflammation with high levels of apoptosis, which seems to lead to a decline of the pulmonary and peripheral muscle function. Understanding these mechanisms may be a way to establish new therapeutic strategies for management of COPD.

Monitoramento de eventos adversos em ambiente hospitalar: relato de farmacovigilância, São Paulo / Monitoring of adverse events in hospitals: report of pharmacovigilance, São Paulo

Introdução: O percentual de internações hospitalares devido às reações adversas (RA) a medicamentos em alguns países é cerca de 10% (OPAS/OMS) e acarreta gastos adicionais para o sistema de saúde. Objetivo: Determinar medicamentos mais envolvidos em RA e as RA mais comuns. Métodos: Realizou-se um monitoramento descritivo de RA em hospital privado de São Paulo, de 2004 a 2008, em 197 leitos, totalizando 100 notificações. Dados descritos em frequência (n de RA relatadas). Resultados: Os medicamentos mais envolvidos em RA foram:cefalosporinas (13%) e quinolonas (12%). As RAs foram: rash cutâneo (20%), prurido (13%), hiperemia (12%), náusea (10%), tremores (9%), placas eritematosas (6%), etc. Observou-se que 61% dos indivíduos com RA são do sexo feminino. Conclusão: Sugere-se uma atitude positiva em farmacovigilância, para que a notificação se torne rotina. Verificou-se que houve crescimento das notificações. Pacientes do sexo feminino apresentaram mais RA e os antibióticos foram os medicamentos com maior RA.

Introduction: According to PAHO/WHO, the hospital admissions? due to adverse drug reactions (ADR) in some countries is around 10%, resulting in additional costs for health system. Objective: To determine which drugs are involved in adverse drug reactions and the most common reactions. Methods: We conducted a descriptive monitoring of ADR in a private hospital in São Paulo (Brazil), from 2004 to 2008, in 197 beds, totaling 100 notifications. Data described in frequency (n ADR reported). Results: The drugs most commonly involved in ADR were cephalosporins (13%) and quinolones (12%). The adverse reactions were rash (20%), pruritus (13%), redness (12%), nausea (10%), tremors (9%), erythematous plaques (6%), etc. We observed that 61% of individuals with ADR are female. Conclusion: Achieve the development of positive attitude towards pharmacovigilance among healthcare professionals to ADR becomes accepted and understood. There was an increase in notifications, antibiotics are involved in ADR and female have more ADR.

Repercussões musculares do uso de glicocorticóides na distrofia muscular de Duchenne e na DPOC / Muscle implications of gucocorticoid treatment for Duchenne muscular dystrophy and for COPD

Os glicocorticóides sintéticos são usados terapeuticamente de forma eficaz para uma ampla variedade de condições que exigem modulação imunológica ou inflamatória, incluindo o tratamento de distrofias musculares e doenças respiratórias como asma e doença pulmonar obstrutiva crônica (DPOC). A distrofia muscular do tipo Duchenne é uma doença geneticamente determinada que se manifesta por fraqueza progressiva, degeneração e atrofia dos músculos esqueléticos. Muitas intervenções farmacológicas foram propostas, entretanto, até o momento, os glicocorticóides são os únicos fármacos que determinam melhora substancial para estes pacientes. Já na DPOC, o tratamento com glicocorticóide é efetivo e amplamente difundido, porém as reações adversas da terapia sistêmica ou inalatória com o uso destes fármacos podem repercutir no decurso da doença e na qualidade de vida dos pacientes. Neste sentido, diante das modulações fisiológicas, efeitos terapêuticos e adversos que os glicocorticóides promovem, o presente estudo busca avaliar os efeitos terapêuticos e adversos promovidos pela terapia crônica ou repetitiva de glicocorticóides na distrofia muscular de Duchenne e na DPOC, com ênfase nos sítios musculares, os quais são diretamente afetados pela sua utilização e constituem um importante alvo reabilitador do manejo fisioterapêutico.

Synthetic glucocorticoids are used therapeutically for a wide variety of conditions that require immune modulation and/or inflammation, including treatment of muscular dystrophy and respiratory diseases like asthma and COPD. Duchenne muscular dystrophy is a genetically determined disease which is characterized by progressive weakness, degeneration and atrophy of skeletal muscles. Many pharmacological interventions have been proposed, however, glucocorticoids are the only drugs that determine substantial improvement for these patients. In COPD, the treatment with glucocorticoids is effective and widespread, but the side effects of systemic or inhaled therapy could have repercussions in the course of the disease and in the quality of life of the patients. In this sense, considering modulations of physiological, therapeutic and adverse effects promoted by glucocorticoids, this study aims to evaluate the therapeutic and adverse effects related by chronic or recurrent treatment of glucocortícoids for Duchenne muscular dystrophy and COPD, with emphasis on muscle sites, which are directly affected by its use, and constitute an important target of rehabilitation therapy management.

Penetration of cefuroxime in subcutaneous tissue during coronary artery bypass grafting surgery.

A sensitive and rapid HPLC assay for determining cefuroxime penetration in the subcutaneous tissue near to surgical incision of patients submitted to coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (CPB) was performed. Blood and subcutaneous tissue samples were collected from 14 patients, in four periods during surgery. The analytical method presented linearity from 0.5 to 100 microg/g, LOQ=0.50 microg/g, LOD=0.25 microg/g, intra- and interday precision (%CV) ranged from 4.9 to 8.9% and 6.4 to 9.9%, respectively, and intra- and interday accuracy expressed as % of the nominal concentration ranged from 87.1 to 104.6% and 94.8 to 103.8%, respectively (mean of three concentrations). Relative recovery was 98.4%. Tissue/plasma ratios obtained for CPB and non-CPB were, respectively: 14.6% vs 19.0% (0.6 h); 15.7% vs 15.7% (2.1 h); 22.5% vs 19.9% (3.6 h); 15.7% vs 18.8% (4.5 h). Data obtained indicate that tissue/plasma ratio remains unchanged in CPB and non-CPB patients during all period of surgery and the CPB does not affect the penetration of cefuroxime in tissues close to the surgical wound.

Perfil da prescrição de antibioticoprofilaxia em exodontia por cirurgiões dentistas da cidade de São Paulo / Profile of antibiotic prophylaxis prescription in exodontia by dentists from the city of São Paulo

Realizou-se um estudo prospectivo, com a aplicação de um questionário estruturado a 100 dentistas da cidade de São Paulo, para se avaliar a prescrição odontológica, a especialização do dentista, idade, tempo de atuação clínica e se o mesmo fez algum curso de reciclagem em farmacologia, após a graduação. Os resultados mostraram uma grande variação no esquema terapêutico, quanto ao fármaco e quanto à necessidade da prescrição. A maioria dos pesquisados não realizou reciclagem em farmacologia. Dentre aqueles que relataram ter realizado algum curso de reciclagem, foi observada uma similaridade na prescrição: amoxicilina: 500mg a cada 8 horas, por 7 dias. Entretanto, apenas 9,3% dos entrevistados relataram utilizar a antibioticoprofilaxia recomendada pela American Heart Association (AHA). A grande variabilidade para indicação da antibioticoprofilaxia, seja quanto à escolha do fármaco, esquema terapêutico ou situações em que devam ser prescritos, demonstra que a padronização do uso destes fármacos na prática clínica odontológica deve ser levada em consideração, evitando sua administração de forma equivocada ou desnecessária para seus pacientes.

A prospective study was carried out, applying a structured questionnaire to 100 dentists in the city of São Paulo, to evaluate the prescription, the expertise, age, clinical practice, experience time and if they had done any recycling course in pharmacology after graduation. A great variation in the therapeutic scheme and in the drug chosen was observed, as well as the prescription necessity. The majority of the dentists had not done recycling courses in pharmacology and great divergences between the prescriptions were observed. Among those who had reported to have done some recycling course, were observed similarities in the choice of the drug: amoxicillin 500mg every 8 hours, for 7 days. Only 9.3% reported applying the dose scheme recommended by the American Heart Association (AHA): amoxicillin 2g, single dose, 1h before the surgery. The great variability in the antibiotic prophylaxis prescription, such as drug choice and therapeutic scheme, shows that the antibiotic standardization in dentistry clinical practice should be considered to avoid unnecessary or incorrect antibiotic administration in their patients.

Esofagite química e ulcerações esofágicas associadas ao uso de alendronato sódio / Esophageal quimical and ulceration esophageal associated to the use of alendronate of sodium

Objetivo: O presente trabalho enfoca o perfil do paciente que utiliza o alendronato de sódio e suas possíveis queixas. Material e Métodos: Aplicação de questionário estruturado para pacientes atendidos em farmácias com manipulação e drogarias, nas regiões de Santana e Guarulhos, São Paulo. Critérios de inclusão: uso de alendronato de sódio, ambos os sexos, 45 e 80 anos. Variáveis observadas: características demográficas, origem da prescrição, prescritor, padrões de uso e queixas dos pacientes. Resultados: Pacientes entre 60-70 anos de idade, sexo feminino, praticantes de alguma atividade física. 88% relatam seguir a posologia adequadamente, 13% apresentaram queixas como: azia (mais prevalente), dor de garganta ou dificuldade ao engolir, dor no estômago e gases. A dose mais comum de alendronato de sódio foi 70mg uma vez por semana. Grande parcela dos pacientes faz uso do medicamento há mais de um ano e de outros concomitantes: antiinflamatórios (31%), analgésicos (25%), anti-hipertensivos (46%), hormônios (18%) entre outros. Conclusão: O uso incorreto do alendronato está relacionado com as reações adversas gástricas, pudemos observar que nem sempre o uso correto reduz a incidência de problemas esofágicos, portanto, tais queixas poderiam estar relacionadas ao fármaco em si.

Freqüência de uso de inibidores de fosfodiesterase-5 por estudantes universitários / Use of phosphodiesterase-5 inhibitors by college students / Uso de inhibidores de fosfodiesterasa-5 por estudiantes universitários

O objetivo do estudo foi identificar o uso de inibidores da fosfodiesterase-5 por estudantes universitários da cidade de São Paulo (SP), em 2006. Alunos do sexo masculino (n=360) responderam questionário sobre diagnóstico de disfunção erétil, freqüência e motivo do uso, medicamento utilizado, existência de prescrição médica e relato de efeitos adversos. Os resultados mostraram que 53 (14,7 por cento) dos alunos já haviam utilizado esses medicamentos, dos quais 53 por cento relataram uso de sildenafila, 37 por cento tadalafila e 10 por cento vardenafila, adquiridos sem prescrição médica ou diagnóstico de disfunção erétil. Os principais efeitos adversos relatados foram cefaléia (23 por cento) e rubor facial (10 por cento), e as principais motivações para uso foram a curiosidade (70 por cento) e potencialização da ereção (12 por cento).

Use of phosphodiesterase-5 inhibitors by college students.

The objective of this study was to identify the use of phosphodiesterase type 5 inhibitors among university students from the city of Sao Paulo (SP) in Brazil. Male students (n=350) replied to a questionnaire about diagnosis of erectile dysfunction, the frequency and reason for the use of phosphodiesterase type 5 inhibitors, the specific medication used, whether their use was accompanied by a medical prescription and any reported side-effects. The results shows that a total of 53 (14.7%) students had already used this kind of medication without a prescription or medical diagnosis for erectile dysfunction, of which 53% reported using sildenafil, 37% tadalafil and 10% vardenafil. The main adverse side-effects reported were headache (23%) and flushing (10%) and the main reasons for using the inhibitor were curiosity (70%) and erectile improvement (12%).

Fatores relacionados à prescrição médica de antibióticos em farmácia pública da região Oeste da cidade de São Paulo / Factors related to prescriptions of antibiotics in a public pharmacy in the Western region of the city of São Paulo

Os antibióticos são comumente utilizados para melhorar uma infecção estabelecida e possuem a finalidade de eliminar ou impedir o crescimento bacteriano. Os riscos mais importantes relacionados ao seu uso são: reações adversas, resistência bacteriana e possíveis interações medicamentosas. Foram realizadas entrevistas com os pacientes para observar o entendimento dos mesmos sobre o uso do antibiótico e tratamento. 38,3 por cento dos pacientes são menores de 18 anos e a maioria é do sexo feminino. Um terço não compreende diagnóstico ou posologia e a maioria consultou-se com um clínico geral. Ainda há resistência na prescrição do nome genérico. Cerca de 8 por cento das receitas continham interação medicamentosa. Grande parte dos tratamentos pode estar comprometida pelo não entendimento do paciente ou presença de interação medicamentosa. A eficácia do tratamento depende de todos os profissionais de saúde, sendo necessário treinamento a esses profissionais tanto para conhecimento próprio quanto para atenção farmacêutica.

The use of antibiotics in the treatment of established infections for inhibiting or abolishing the growth of microorganism is very common. The risks related to their use include side effects, drug resistance and potential drug-drug interactions. A structured questionnaire was applied to patients in order to collect information about their understanding of the treatment and of how to use the antibiotic. As to the profile of the patients, 38.3 percent are younger than 18 years and most are females. One third does not understand the diagnosis or prescribed dosage and most of the patients had consulted with the general practitioner. Prescriptions of generic drugs continue rare, probably due to the physicians' resistance to prescribe this kind of medication. About 8 percent of prescriptions involved drug-drug interactions. Many treatments are compromised due to the lack of information provided to the patient or to drug-drug interactions. The efficiency of a treatment depends on all health professionals involved, who need to be adequately trained for providing effective pharmacy care.

[Factors related to prescriptions of antibiotics in a public pharmacy in the Western region of the city of São Paulo]. / Fatores relacionados à prescrição médica de antibióticos em farmácia pública da região Oeste da cidade de São Paulo.

The use of antibiotics in the treatment of established infections for inhibiting or abolishing the growth of microorganism is very common. The risks related to their use include side effects, drug resistance and potential drug-drug interactions. A structured questionnaire was applied to patients in order to collect information about their understanding of the treatment and of how to use the antibiotic. As to the profile of the patients, 38.3% are younger than 18 years and most are females. One third does not understand the diagnosis or prescribed dosage and most of the patients had consulted with the general practitioner. Prescriptions of generic drugs continue rare, probably due to the physicians' resistance to prescribe this kind of medication. About 8% of prescriptions involved drug-drug interactions. Many treatments are compromised due to the lack of information provided to the patient or to drug-drug interactions. The efficiency of a treatment depends on all health professionals involved, who need to be adequately trained for providing effective pharmacy care.

Perioperative cefuroxime pharmacokinetics in cardiac surgery.

OBJECTIVE: The objective was to investigate the plasma levels and to compare the pharmacokinetics of cefuroxime during and after surgery in adult patients with elective indication for coronary artery bypass grafting. METHODS: Seventeen patients received three 1.5-g bolus IV doses of cefuroxime, one every 12 hrs. Serial blood samples (3 mL) were collected 1, 3, 6, 9, and 12 hrs after the first dose (given during the intervention) and after the second and third doses (postsurgery). Blood samples were centrifuged and stored frozen until being assayed. For assessment of the cefuroxime plasma levels by liquid chromatography, only 200 microL of plasma were required. Determination of cefuroxime plasma levels was followed by a pharmacokinetic (PK)-modeling using PK Solutions 2.0 software. RESULTS: The kinetic parameters obtained remained unchanged after the first, second, and the third dose as follows: elimination half-life: 1.8 h, 1.9 h, and 1.8 h; clearance: 1.4, 1.5, and 1.5 mL/min/kg, respectively. Additionally, the apparent volume of distribution did not change during and after the intervention: 0.19, 0.25, and 0.22 L/kg, after the first, second, and the third dose, respectively. Since the drug has a low volume of distribution, plasma levels obtained after a 1.5-g IV bolus injection of cefuroxime decreased rapidly due to the high plasma clearance, with a consequent short half-life. CONCLUSIONS: The kinetic disposition of cefuroxime remains unaltered in patients undergoing coronary artery bypass grafting; to reduce the fluctuation in plasma concentrations so that the antibiotic prophylaxis in the peri-operative period is guaranteed, the dose regimen should be reviewed.

Perioperative cefuroxime pharmacokinetics in cardiac surgery

OBJECTIVE: The objective was to investigate the plasma levels and to compare the pharmacokinetics of cefuroxime during and after surgery in adult patients with elective indication for coronary artery bypass grafting. METHODS: Seventeen patients received three 1.5-g bolus IV doses of cefuroxime, one every 12 hrs. Serial blood samples (3 mL) were collected 1, 3, 6, 9, and 12 hrs after the first dose (given during the intervention) and after the second and third doses (postsurgery). Blood samples were centrifuged and stored frozen until being assayed. For assessment of the cefuroxime plasma levels by liquid chromatography, only 200 æL of plasma were required. Determination of cefuroxime plasma levels was followed by a pharmacokinetic (PK)-modeling using PK Solutions 2.0 software. RESULTS: The kinetic parameters obtained remained unchanged after the first, second, and the third dose as follows: elimination half-life: 1.8 h, 1.9 h, and 1.8 h; clearance: 1.4, 1.5, and 1.5 mL/min/kg, respectively. Additionally, the apparent volume of distribution did not change during and after the intervention: 0.19, 0.25, and 0.22 L/kg, after the first, second, and the third dose, respectively. Since the drug has a low volume of distribution, plasma levels obtained after a 1.5-g IV bolus injection of cefuroxime decreased rapidly due to the high plasma clearance, with a consequent short half-life. CONCLUSIONS: The kinetic disposition of cefuroxime remains unaltered in patients undergoing coronary artery bypass grafting; to reduce the fluctuation in plasma concentrations so that the antibiotic prophylaxis in the peri-operative period is guaranteed, the dose regimen should be reviewed.

OBJETIVO: Investigar os níveis plasmáticos e comparar a farmacocinética da cefuroxima durante e após cirurgia de revascularização do miocárdio. MÉTODOS: Dezessete pacientes receberam três doses intravenosas de 1,5 g de cefuroxima, a cada 12 horas. Foram coletadas amostras de sangue nos tempos de 1, 3, 6, 9 e 12 horas após a primeira dose (durante a cirurgia) e após a segunda e terceira dose (administradas após a cirurgia). As amostras de sangue foram centrifugadas e armazenadas congeladas até o momento da análise. Os níveis plasmáticos da cefuroxima foram determinados através de cromatografia líquida, utilizando-se apenas 200 mL de plasma. A determinação da farmacocinética da cefuroxima foi realizada utilizando o software PK-solutions 2.0. RESULTADOS: Todos os parâmetros cinéticos obtidos permaneceram inalterados após a adminstração da 1ª, 2ª e 3ª doses: meia vida de eliminação 1,8h, 1,9h and 1,8h, depuração 1,4, 1,5 and 1,5 mL/min/kg respectivamente. Adicionalmente, o volume aparente de distribuição, não se alterou durante ou após a intervenção: 0,19, 0,25 and 0,22 L/kg, após 1ª, 2ª e 3ª dose, respectivamente. Os níveis plasmáticos obtidos após administração da cefuroxima reduziram rapidamente devido à alta depuração plasmática com conseqüente curta meia-vida plasmática, atingindo valores abaixo da concentração inibitória mínima a partir da 9ª hora da administração. CONCLUSÕES: A disposição cinética da cefuroxima permanece inalterada em pacientes submetidos à cirurgia de revascularização do miocárdio, e com vistas à redução da flutuação no período perioperatório, o regime de dose para a antibioticoprofilaxia poderia ser revisto.

Micrométodo para quantificação de cefuroxima em plasma através da cromatografia líquida de altav eficiência. Aplicação na profilaxia de pacientes submetidos à cirurgia cardíaca / Micromethod for plasma cefuroxime quantification through high performance liquid chromatography. Application to the prophylaxy of patients submitted to cardiac surgery

O objetivo desta investigação foi desenvolver metodologia analítica adequada, simples e precisa para quantificação da cefuroxima plasmática para controle de pacientes cirúrgicos em profilaxia com esse antimicrobiano. Realizou-se a quantificação da cefuroxima na matriz biológica através da cromatografia líquida de alta eficiência CLAE-UV. Apenas 200 µL de plasma foram requeridos para a precipitação das proteínas com acetonitrila. Empregou-se coluna de fase reversa (NovaPak C18, 150 x 3,9 mm, 4 µm) e os picos foram eluídos isocraticamente com fase móvel (tampão acetato 0,375 M, pH 5,0 e acetonitrila, 96:4, v/v, 0,8 mL/min) em 12,5 min (cefuroxima) e 4,0 min (vancomicina, padrão interno) sendo os picos monitorados a 280 nm...