Biodisponibilidade da amoxicilina. Estudo ex vivo em ratos

Orientador: Francisco Carlos GroppoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Embora existam vários relatos a respeito da resistência bacteriana à amoxicilina, são várias as situações, na Medicina e na Odontologia, onde seu emprego é tido como de primeira escolha. Este fármaco é um importante componente do arsenal terapêutico antimicrobiano. A recente reedição das normas para profilaxia da endocardite bacteriana é um exemplo claro deste fato. Apesar de existir concordância de que, para que seja efetivo, a amoxicilina ou um outro antibiótico qualquer devam ultrapassar em níveis séricos a concentração inibitória mínima de um dado patógeno, não é no sangue que a maioria das infecções se encontra. Poucos são os dados a respeito da concentração tissular que a amoxicilina atinge, uma maior ênfase sempre é dada aos níveis séricos da droga. Este trabalho teve por objetivo estudar a concentração tecidual da amoxicilina. Para tanto, utilizou-se 60 ratos, nos quais foram implantadas, dorsal e subcutâneamente, quatro esponjas de PVc. Após decorridos 14 dias da implantação, os animais receberam uma suspensão de amoxicilina, por via intragástrica, na dose de 40mg/kg. Decorridos 15 min, 30 min, 1, 11/2, 2, 4, 6, 8, 10 e 12 horas após a administração, as amostras de sangue, bem como os tecidos granulomatosos foram colhidos. As amostras de sangue foram centrifugadas e 10 µLdos soros obtidos foram distribuídos em discos de papel e, assim como os tecidos, foram dispostos em placas de Petri, contendo ágar Mueller Hinton previamente inoculado com 108 u.f.c./mL de Staphy/ococcus aureus (ATCC 25923). Após um período de incubação de 18 horas, os halos de inibição foram medidos e anotados para posterior análise. Previamente, foi construída uma curva de regressão, com o halo de inibição em função dos logaritmos de concentrações conhecidas da droga. Observou-se que o fármaco atingiu níveis acima das concentrações inibitória e bactericida mínimas, no período compreendido entre 30 min e 8 horas após a administração, tanto no sangue quanto no tecido. Os resultados levam a crer que esquemas posológicos de 6/6 horas ou 8/8horas são válidos para manter as concentrações antimicrobianas em níveis suficientesAbstract: Although there are severa I reports regarding the bacterial resistance to amoxicillin, it is used as a first choice therapy in medicine and dentistry. The recent edition of the guidelines for the prevention of bacterial endocarditis is a clear example of this. In spite of it is widely accept that every antibiotic should achieve higher serum levei than the minimum inhibitory concentration for a given bacteria, the blood is not the place where the majority of the infections occur. There are few data about the tissue concentration that the amoxicillin reaches; a greater importance is given to the serum levels of this drug. This aim of this paper was to study the tissue concentration of the' amoxicillin. Sixty male rats were implanted the back with 4 PVC sponges. After 14 days of the implantation, the animais received orally 40mg/kg of amoxicillin suspension and were sacrificed in groups of 6 at 15 min, 30 min, 1, 1112, 2, 4, 6, 8, 10 and 12 hours after the administration. Blood samples and granulomatous tissues were collected. After the centrifugation of blood samples, 10 I-IL of sera were distributed in paper disks and, as well the granulomatous tissue were disposed in Petri dishes with Mueller Hinton agar inoculated with 108 c.f.u. of 5taphy/ococcus aureus (ATCC 25923). After 18 hours of incubation the inhibition zones were measured and scored for analysis. A regression curve with the inhibition zones versus the logarithm concentrations of amoxicillin was previously done. It was observed that the drug achieved in blood and tissue concentrations above the minimum inhibitory and bactericide concentrations ones within the period of 30min and 8 hours after the administration. It was concluded that with the dose studied the intervals of 6/6 hours or 8/8 hours would be adequate to keep sufficient levels of the antibioticMestradoFarmacologiaMestre em Ciência

Concentrações plasmaticas e salivares e efeito sobre a microbiota oral de duas formulações de amoxicilina : estudo em voluntarios sadios

Orientador: Francisco Carlos Groppo, Pedro Luiz RosalenTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: As concentrações de amoxicilina (AMO)em plasma e saliva e seus efeitos na microbiota oral de voluntários sadios foram analisados, em um estudo aberto, de forma aleatória, cruzado com dois períodos. AMO875 mg (Amoxicilina-EMS- medicamento teste e Amoxil@- medicamentoreferência) foi administrada para todos os voluntários com 1 semana de intervalo entre as doses. Amostras de plasma e saliva foram colhidas em um intervalo de até 12h após a administração. As concentrações plasmáticas de AMOforam obtidas por cromatografia líquida e espectrometria de massas com ionização por electrospray (LC-ESI-MS). As concentrações de amoxicilina em saliva foram analisadas por cromatografia líquida de alta eficiência (HPLC).As contagens dos microrganismos totais, anaeróbios e estreptococos foram obtidas em diferentes condições de cultura. ASC foi calculada pelo método de extrapolação dos trapezóides. Cmaxe Tmaxforam compilados dos dados de concentração-tempo. Análise de variância foi realizada usando dados logaritmicamente transformadospara ASCo-inf, ASCO-12h, Cmax e não transformados para Tmax.As médias (:1:dp) para ASCO-12h (jJg.h.mL-1),ASCo-inf (jJg.h.mL-1),Cmax (jJg.mL-1)and Tmax(h), foram respectivamente: 55,42(:1:16,85), 55,42 (:1:16,85), 18,59 (:1:6,3), 2,04(:1:0,75) para o medicamento teste e 51,11 (:1:18,9), 51,29 (:1:19,12), 17,83 (:1:5,86),2,02 (:i:O,87)para o medicamento referência. Intervalos de confiança (90%) para a razão das médias de AMO(testejreferência) para ASCO-12he Cmaxforam: 0,961-1,149 e 0,914 - 1,142, respectivamente. Tanto para as concentrações plasmáticas quanto para as salivares não foram observadas diferenças estatisticamente significantes entre os dois medicamentos (Teste t pareado, p>0.05). As contagens de microrganismos provindos da saliva não mostraram diferenças estatísticas (ANOVAde medidas repetidas, p>0.05) entre as duas formulações durante cada tempo. A partir de 60 min, uma redução estatisticamente significante (ANOVAde medidas repetidas, p<0.05) foi observada para todos os microrganismos. Os dois medicamentos foram considerados bioequivalentes baseado na razão e extensão de absorção e foram eficazes na redução dos microrganismos da microbiota oral avaliados até 12 horasAbstract: The plasmatic and salivary concentration of amoxicillin(AMO)875mg and its effects on oral microbiota in healthy volunteers were assessed in an open, randomized, two-period crossover designo A single 875 mg oral dose of AMO (Amoxicillin-EMS- test formulation and Amoxil@- reference formulation) was administered to ali volunteers observing 1-week intervaI between doses. Blood and saliva samples were collected from pre-dose to 12 h. The concentrations of AMO, in plasma and saliva, were quantified by LC-ESI-MSand LCmethod, respectively. AUC was calculated by the trapezoidal rule extrapolation method. Cmaxand Tmax were compiled from the plasmatic concentration-time data. Streptococci, anaerobe, and total microorganisms' counts were obtained in different culture conditions. The mean values (:1:SD) for AUCO-12(lh1g.h.mL-1),AUCO-í(nlf1g.h.mL-1),Cmax(l1g.mL-1) and Tmax(h), were respectively: 55.42(:1:16.85), 55.42 (:I:16.85), 18.59 (:I:6.3), 2.04{:I:0.75) concerning the test formulation and 51.11 (:I:18.9), 51.29 (:I:1,9.12), 17.83 (:I:5.86), 2.02 (:1:0.87) concerning the reference formulation. Confidence intervals (90%) of amoxicillinmeans of AUCO-12ahnd Cmaxratios (testjreference) were: 0.961 - 1.149 and 0.914 - 1.142, respectively. No statistically significant differences were observed between the two formulations (t test, p>0.05) regarding AMOplasmatic and saliva concentrations. Saliva microorganisms counts did not show statistical differences (ANOVArepeated measures, p>0.05) between the two groups during each sampling time. Starting at 60 min, a statistically significant decrease (ANOYArepeated measures, p<0.05) was also observed for all microorganisms. Both formulations were bioequivalent based on both the rate and extent of absorption, and were effective in reduce microorganisms until 12 hoursDoutoradoFarmacologia, Anestesiologia e TerapeuticaDoutor em Odontologi

Isolation and antimicrobial resistance of Staphylococcus aureus isolates in a dental clinic environment

To determine the number of Staphylococcus aureus isolates collected in a dental clinical environment and to determine their susceptibility to antimicrobial agents commonly used in dentistry. Undergraduate clinic of the Dental School of Piracicaba, University of Campinas, Brazil. Sterile cotton swabs were used to collect the samples from dental-chair push buttons, light handles, 3-in-1 syringes, computer Enter keys, doorknobs, and X-ray tubes before, during, and after clinical procedures. These samples were spread on brain-heart infusion agar and were incubated at 37 degrees C for 24 hours. The resulting S. aureus isolates were counted and classified using Gram staining and biochemical tests. The counts among the 3 periods and the groups were analyzed by Kruskal-Wallis and Dunn tests (alpha =5%). Commercial paper disks containing widely prescribed antimicrobial agents (beta-lactams, macrolides, clindamycin, and vancomycin) were used to perform the antimicrobial susceptibility tests. An increase in the number of microorganisms was observed during clinical procedures (P<.05). The highest bacterial resistance rates were observed for the beta -lactam group. All isolated strains were sensitive to vancomycin, and 2% of them were resistant to methicillin. Clinical procedures increased the number and proportion of antimicrobial-resistant S. aureus isolates dispersed in a dental clinical environment. The present study highlights the need to establish strategies to prevent emergence of drug-resistant bacterial strains in dental settings.To determine the number of Staphylococcus aureus isolates collected in a dental clinical environment and to determine their susceptibility to antimicrobial agents commonly used in dentistry. Undergraduate clinic of the Dental School of Piracicaba, University of Campinas, Brazil. Sterile cotton swabs were used to collect the samples from dental-chair push buttons, light handles, 3-in-1 syringes, computer "Enter" keys, doorknobs, and X-ray tubes before, during, and after clinical procedures. These samples were spread on brain-heart infusion agar and were incubated at 37 degrees C for 24 hours. The resulting S. aureus isolates were counted and classified using Gram staining and biochemical tests. The counts among the 3 periods and the groups were analyzed by Kruskal-Wallis and Dunn tests (alpha =5%). Commercial paper disks containing widely prescribed antimicrobial agents (beta-lactams, macrolides, clindamycin, and vancomycin) were used to perform the antimicrobial susceptibility tests. An increase in the number of microorganisms was observed during clinical procedures (P<.05). The highest bacterial resistancerates were observed for the beta -lactam group. All isolated strains were sensitive to vancomycin, and 2% of them were resistant to methicillin. Clinical procedures increased the number and proportion of antimicrobial-resistant S. aureus isolates dispersed in a dentalclinical environment. The present study highlights the need to establish strategies to prevent emergence of drug-resistant bacterial strains in dental settings28218519

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Abstract The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA