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−1vs. 121 [103, 149] mg · h · l−1, 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. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Introdução: Problemas associados ao uso de medicamentos são frequentes, ocasionando impacto na Saúde. Prevenir e minimizar requer ações no processo da farmacoterapia para redução de erros de medicação. No entanto, há necessidade de mudanças da prática profissional. Objetivo: Conhecer o processo de transformação do profissional e a implementação das atividades clínicas. Métodos: Estudos sobre os serviços farmacêuticos clínicos no Brasil nos últimos anos. Resultados: Atividades de farmácia clínica no Brasil ocorrem de forma desigual nas regiões. Ressalta-se a importância do registro das atividades que sistematiza o acompanhamento da terapia medicamentosa e possibilita avaliar necessidade, segurança e efetividade da utilização de medicamentos, proporcionando resultados favoráveis. No entanto, as dificuldades na implementação dos serviços clínicos comprometem o desempenho do farmacêutico. Conclusão: importância do farmacêutico nos Serviços de Farmácia Clínica, de forma a promover o acesso e uso racional de medicamentos e prevenção de eventos adversos, com melhoria da qualidade de vida.

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.

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.

Objetivo: Descrever o perfil epidemiológico dos pacientes com COVID-19 que evoluíram para casos mais graves da doença e necessitaram de internação na Unidade de Terapia Intensiva (UTI) de um hospital de Juiz de Fora – MG e correlacionar tais características com o desfecho clínico do paciente.  Métodos: Trata-se de um estudo de natureza observacional e de tipologia transversal, em que foram analisados prontuários de pacientes com COVID-19 internados na UTI de um hospital de Juiz de Fora - MG, durante abril de 2020 a outubro de 2020. Resultados: Maiores taxas de internação foram verificadas no sexo masculino (62,7%) e a comorbidade mais frequentemente observada foi a hipertensão arterial sistêmica (67,3%). O teste qui-quadrado de independência mostrou que há associação entre óbito e a faixa etária do paciente. A presença de comorbidades não se mostrou como um fator preditivo para maior gravidade, visto que os testes de ANOVA não mostraram diferenças estatísticas significativas, sendo o tamanho amostral um importante fator limitante para essa análise. Conclusão: O maior risco de ocorrência de casos graves e de óbitos por COVID-19 foi observado em indíviduos idosos, o que posibilta o desenvolvimento de condutas profissionais adequadas para esse grupo específico, prevenindo desfechos desfavoráveis.