Evaluation of physical-mechanical properties, antibacterial effect, and cytotoxicity of temporary restorative materials

Abstract The objective of this study was to compare selective physical-mechanical properties, antibacterial effects and cytotoxicity of seven temporary restorative materials (TRM): five resin-based materials [Bioplic (B), Fill Magic Tempo (FM), Fermit inlay (F), Luxatemp LC (L) and Revotek LC (R)], and zinc oxide-eugenol cement (IRM) and glass ionomer cement (GIC) as the controls. Material and methods The physical-mechanical properties were evaluated by determining microleakage (ML), ultimate tensile strength (UTS) and Shore D hardness (SDH). In addition, the polymerization rate (Pr-1), depth of cure (DC), water sorption and solubility (WS/SL) were evaluated. The antimicrobial effects of the materials were assessed by biofilm accumulation of Streptococcus mutans (BT) and the direct contact test (DCT) by exposure to Enterococcus faecalis for 1 and 24 h, and cytotoxicity by MTT assay. The data were analyzed by ANOVA or Kruskall-Wallis tests, and a complementary post-hoc method (p<0.05). Results Group B, followed by FM and GIC had significantly lower percentages of microleakage in comparison with the other groups; Groups FM and L showed the highest WS, while Groups R and FM showed the significantly lowest SL values (p<0.05). Group R showed the statistically highest UTS mean and the lowest DC mean among all groups. Group F showed the lowest S. mutans biofilm accumulation (p=0.023). Only the Group L showed continued effect against E. faecalis after 1 h and 24 h in DCT. The L showed statistically lower viability cell when compared to the other groups. Conclusions These findings suggest the antibacterial effect of the temporary materials Fill Magic and Bioplic against S. mutans, while Luxatemp showed in vitro inhibition of S. mutans biofilm accumulation and E. faecalis growth. Regarding the cell viability test, Luxatemp was the most cytotoxic and Fill Magic was shown to be the least cytotoxic.

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Abstract Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m2/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m2/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m2/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p < 0.001). A dose of 27 mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

Parámetros farmacocinéticos de gentamicina en recién nacidos de término: ¿Es necesario monitorizar en forma sistemática sus concentraciones plasmáticas? / Gentamicin pharmacokinetics in term newborn: ¿Is it necessary to systematically monitor plasmatic levels?

Background: Gentamicin is indicated as empiric treatment for neonatal sepsis. Plasmatic levels dosification of gentamicin is a common practice. The relationship between peak plasma concentration (Cmáx) with minimum inhibitory concentration (MIC) (Cmáx/MIC) is the parameter that best predicts treatment efficacy. Aim: To determine pharmacokinetics of gentamicin in term newborn infants. Methods: Term newborn infants receiving gentamicin, without critical illness in which plasmatic levels of gentamicin was performed were included. Elimination clearance (Cl) elimination half-life (t½) and volume of distribution (Vd) were calculated. In each case the value of Cmax/MIC parameter was calculated, considering a MIC value of 1 μg/mL for Escherichia coli. Results: Thirteen newborns were included. The mean PK values were Cl: 0.26 mL/hour, Vd: 0.54 L/kg and t½: 6.8 h. Cmax/MIC was > 8 in 6 newborns. Conclusions: Pharmacokinetic parameters of gentamicin are predictable in term newborn infants. With gentamicin doses normally used Cmax/MIC values reached 8 in 6 newborns. It is necessary to review the usefulness of plasma drug monitoring and gentamicin dosage in this group of newborns.

Introducción: Gentamicina es utilizada como tratamiento empírico en la sepsis neonatal. El monitoreo de su concentración plasmática es una práctica frecuente. La relación entre la concentración plasmática máxima (Cmax) y la concentración inhibitoria mínima (Cmax/ CIM) es el parámetro que mejor predice la eficacia. Objetivo: Determinar los parámetros farmacocinéticos (FC) de gentamicina en recién nacidos (RN) de termino. Material y Métodos: Se incluyeron RN de término, sin enfermedad crítica, en tratamiento con gentamicina (4 mg/kg/24 h) en los que se realizó monitoreo de su concentración plasmática. Se determinaron: clearence de eliminación (Cl), vida media de eliminación (t½) y volumen de distribución (Vd). Se estimó la Cmax/CIM, considerando una CIM de 1 μg/mL para Escherichia coli. Resultados: Participaron 13 RN. La media de Cmax fue 8,19 μg/mL y de Cmin 0,73 μg/mL. La media de los parámetros farmacocinéticos fue: Cl 0,26 mL/h, Vd 0,54 L/kg, t½ 6,8 h. La razón Cmáx/CIM fue ≥ 8 en 6 de los 13 RN. Conclusiones: Los parámetros FC de gentamicina en RN de término, sin enfermedad crítica, son predecibles. La posología habitual no permitió obtener valores de Cmax/CIM > 8 en todos los casos. Es necesario revisar la necesidad de monitorizar su concentración plasmática en forma sistemática y la posología de gentamicina en este grupo de pacientes.

Monitoreo terapéutico de vancomicina intravenosa en una unidad de paciente crítico pediátrico / Therapeutic monitoring of intravenous vancomycin in a pediatric critical care unit

Background: In critically ill pediatric patients vancomycin distribution and elimination is altered underscoring the need for pharmacokinetic monitoring; however the therapeutic trough ranges have not been validated for children. Objective: To describe the pharmacokinetics of intravenous vancomycin in critically ill pediatric patients using plasmatic vancomycin monitoring. Methods: Retrospective, descriptive study performed in a paediatric critical care unit. Vancomycin serum levels (Cmin and Cpeak), t ½ and Vd were determined in 1 month to 12 year old patients receiving ≥ 40 mg per-kg-per day. Plasmatic levels were measured at therapy onset and during follow up, evaluating the proportion of trough level determinations within therapeutic range, the average trough concentration, and the Cpeak achieved. Results: A total of 65 plasmatic vancomycin monitorings were analysed in 45 patients. The average values for Ctrough, Cpeak, t1/2 and Vd were 10.4 μg/mL, 22.7 μg/mL, 3,1 h and 0.7 L/kg, respectively. An average dose of 47,1 mg/kg/day achieved initial Ctrough levels < 10 mg/mL in 60% of patients (n = 27), between 10 and 14,9 μg/mL in 22,2% (n = 10), between 15 to 20 μg/mL in 4% (n: 2), and > 20 μg/mL in 13,3% (n: 6). Conclusions: Vancomycin doses of 40 mg/kg/day are insufficient for critically ill paediatric patients without renal failure. A higher starting dose and monitoring of plasma levels must be considered in this population.

Introducción: Los pacientes críticos pediátricos presentan alteraciones en la distribución y eliminación de vancomicina, lo que hace necesaria su monitorización terapéutica; sin embargo, los rangos basales óptimos no han sido validados en niños. Objetivo: Describir el monitoreo terapéutico de vancomicina intravenosa en pacientes críticos pediátricos, a través de medición de concentraciones plasmáticas terapéuticas. Metodología: Estudio descriptivo, retrospectivo, en una Unidad de Paciente Crítico Pediátrica. Se analizaron concentraciones plasmáticas de vancomicina Cbasales y Cpico, en niños entre 1 mes y 12 años de edad, que recibieron dosis ≥ 40 mg/kg/día. Se registraron concentraciones plasmáticas iniciales y de seguimiento, evaluándose la proporción de concentraciones sanguíneas basales en rango terapéutico, la concentración basal promedio y el Cpeak alcanzado. Resultados. Se analizaron 65 monitoreos terapéuticos, correspondientes a 45 pacientes. Los valores promedio de Cbasal, Cpico, t1/2 Vd fueron 10,4 μg/mL, 22,7 μg/mL, 3,1 h y 0,7 L/kg, respectivamente. Las Cbasales iniciales de los 45 pacientes, usando dosis promedio de 47,1 mg/kg/ día, se encontraron en 60% (n: 27) de los casos < 10 μg/mL, entre 10 y 14,9 μg/mL en 22% (n: 10), en 46% entre 15 y 20 μg/mL (n: 2) y en 13,3% (n: 6) fueron > 20 μg/mL. Conclusión: Vancomicina en dosis de 40 mg/kg/día, es insuficiente para pacientes pediátricos críticos sin disfunción renal, por lo que parece recomendable comenzar con dosis mayores y realizar monitoreo terapéutico de concentraciones plasmáticas en estos casos.

Vancomicina en infusión continua en pacientes pediátricos críticos / Continuous infusion of vancomycin in pediatric critical care

La administración de vancomicina en infusión continua es una estrategia de tratamiento posible en pacientes críticos que no alcancen niveles plasmáticos adecuados. Existe escasa bibliografía acerca de este tipo de administración. Se presentan 6 niños (2 meses a 7 años; 4 varones y 2 mujeres) que ingresaron en la unidad de cuidados intensivos del Hospital de Pediatría Garrahan con un cuadro clínico de sepsis por Staphylococcus aureus resistente a la meticilina, tratados con vancomicina, en dosis de entre 40 y 60 mg/kg/día cada 8-6 horas. Debido a la evolución clínica no favorable, la persistencia de la fiebre, los cultivos positivos y los niveles plasmáticos del antibiótico insuficientes, se implementó la infusión continua a 50 mg/kg/día. Todos los pacientes alcanzaron niveles entre 10 y 25 µg/ml, evolucionaron favorablemente y negativizaron los cultivos, sin signos de nefrotoxicidad. El tiempo de tratamiento en infusión continua fue entre 9 y 18 días. La infusión continua de vancomicina fue eficaz en estos pacientes, sin evidencias de nefrotoxicidad asociada.

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.

Synthesis, characterization and biological activity of chelated minerals

Cobalt, Copper and Zinc complexes of amino acids [lysine and glycine] were prepared and characterized by IR, electronic absorption spectra, elemental analysis, magnetic susceptibilities, the differential thermal analysis [DTA] and thermal gravimetric analysis [TGA] of the complexes pointed to their stability. The thermodynamic parameters of the dissociation steps are evaluated. The metal chelates and ligands have been screened for their invitro antibacterial against. Bacillus cereus, Salmonella yeast, E-coli and Staphylococcus. The metal complex [copper glycine] was shown to posses more antibacterial activity than the unchelated ligands. The adsorption ability of complexes to aflatoxin has been studied

Serum Cystatin C Is a Major Predictor of Vancomycin Clearance in a Population Pharmacokinetic Analysis of Patients with Normal Serum Creatinine Concentrations

We developed a population pharmacokinetic model of vancomycin by integrating the effects of cystatin C and other demographic factors in a large population of Korean patients with normal serum creatinine concentrations to elucidate the precise role of serum cystatin C concentrations in the prediction of vancomycin clearance. A population pharmacokinetic model of vancomycin was developed using NONMEM software from a total of 1,373 vancomycin concentration measurements in 678 patients whose serum creatinine concentrations were lower than 1.2 mg/dL. Covariate selection revealed that cystatin C was the most influential factor and had negative influence (-0.78) in the relationship. Total body weight, sex, age, and serum creatinine were also significantly correlated with the clearance. The estimated intersubject variabilities of clearance and volume of distribution were 24.7% and 25.1%, respectively. A 14-fold difference in predicted trough concentrations was observed according to only cystatin C concentrations in a population of simulated individuals with median demographic characteristics. The use of serum cystatin C as marker of vancomycin clearance for more accurate predictions of serum vancomycin concentrations could be useful, particularly among patients with normal serum creatinine concentrations.

Effect of chronic lead intoxication on the distribution and elimination of amoxicillin in goats

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and gamma-glutamyl transferase), blood urea nitrogen, and reactivated delta-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 microg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.

Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection.

Purpose: Recurrent diarrhoea after successful treatment of primary Clostridium difficile associated disease (CDAD) occurs due to bowel flora alterations and failure to mount an effective antibody response. Apart from antibiotics, risk factors include immunosuppressive and acid-suppressive drug administration. Biotherapeutics such as probiotic and epidermal growth factor (EGF) may offer potential effective therapy for CDAD. Materials and Methods: The effect of biotherapeutics in mounting an antibody response against C. difficile toxins was studied in BALB/c mice challenged with C. difficile after pre-treatment with ampicillin, lansoprazole or cyclosporin. Sera from sacrificed animals were estimated for antitoxin IgG by enzyme linked immunosorbent assay. Results: Antitoxin IgG was significantly higher (P<0.05) in C. difficile challenged groups compared to unchallenged controls, but insignificant (P>0.05) in animals in which C. difficile was given after pre-treatment with cyclosporin compared to those without any pre-treatment, or pre-treatment with antibiotic or lansoprazole. In inter-subgroup comparisons also significant anomaly in production of antitoxin IgG was found. The antitoxin IgG levels were raised in animals administered C. difficile after pre-treatment with ampicillin, but lower in animals administered cyclosporin. High levels of antitoxin IgG were also found in the serum samples of animals receiving lansoprazole and C. difficile. Conclusions: Probiotics showed their beneficial effect by boosting the immune response as seen by production of antitoxin IgG. Oral administration of EGF did not affect the immune response to C. difficile toxins as significant increase was not observed in the serum antitoxin IgG levels in any of the groups investigated.

Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients

BACKGROUND: Usual treatment regimens with vancomycin often fail to provide adequate serum levels in patients with severe infections. METHODS: Retrospective analysis of vancomycin trough serum measurements. The following parameters were calculated by Bayesian analysis: vancomycin clearance, distribution volume, and peak estimated concentrations. The area under the concentration curve (AUC) (total daily dose/24 h clearance of vancomycin) was used to determine the effectiveness of treatment through the ratio of AUC/minimum inhibitory concentration (MIC) above 400, using MIC = 1 µg/mL, based on isolates of Staphylococci in cultures. RESULTS: Sixty-one vancomycin trough measurements were analyzed in 31 patients. AUC/MIC > 400 was obtained in 34 out of 61 dosages (55.7%), but the mean vancomycin dose required to achieve these levels was 81 mg/kg/day. In cases where the usual doses were administered (40-60 mg/kg/day), AUC/MIC > 400 was obtained in nine out of 18 dosages (50%), in 13 patients. Trough serum concentrations above 15 mg/L presented a positive predictive value of 100% and a negative predictive value of 71% for AUC/MIC > 400. CONCLUSION: Higher than usual vancomycin doses may be required to treat staphylococcal infections in children with oncologic/hematologic diseases. Since the best known predictor of efficacy is the AUC/MIC ratio, serum trough concentrations must be analyzed in conjunction with MICs of prevalent Staphylococci and pharmacokinetic tools such as Bayesian analysis.

Vancomycin: the need to suit serum concentrations in hemodialysis patients

The vancomycin dose for hemodialysis (HD) patients should be adjusted by monitoring drug serum concentrations. However, this procedure is not available in most health services in Brazil, which usually adopts protocols based on published studies. The trials available are controversial, and several have not been conducted with current dialyzers. This study aimed at assessing the suitability of vancomycin serum concentrations in HD patients at a public hospital. Blood samples of HD patients were collected from November 2006 to May 2007, at time intervals of 48, 96, 120, or 168 hours after vancomycin administration. Drug measurement was performed with polarized light immunofluorescence. Approximately 86 percent of trough vancomycin serum concentrations were below the recommended value, indicating exposure to subtherapeutic doses and a higher risk for selecting resistant microorganisms.

Serum Pro-hepcidin Could Reflect Disease Activity in Patients with Rheumatoid Arthritis

The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6+/-67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28< or =5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.

Solid phase extraction and high performance liquid chromatography for the determination of azithromycin in human plasma.

An effective, selective and sensitive method for the determination of azithromycin in plasma using high performance liquid chromatography-electrochemical detection (HPLC-ECD) extracted by solid phase extraction was developed and validated. Clarithromycin was used as an internal standard. Azithromycin was extracted from 1 ml of plasma using an Oasis HLB solid-phase extraction cartridge and the elution was evaporated to dryness, dissolved in 100 microl mobile phase and 40 microl auto-injected into an HPLC system with a 200 microl loop. The mobile phase was acetonitrile, methanol, phosphate buffer, 0.05M, pH 6.0 (20:20:60, v/v/v) with a flow rate of 1.0 ml/minute. The lower limit of quantitation (LLOQ) was 10 ng/ml without interfering peaks. The calibration curve was linear (r2 = 0.9998) over a concentration range 10 to 400 ng/ml. The accuracy and precision were acceptable. The mean recoveries at 30, 100 and 200 ng/ml were 85.3 +/- 5.5%, 80.1 +/- 6.8% and 82.9 +/- 2.5%, respectively. Azithromycin was stable in plasma for at least 6 hours at room temperature and 6 months storage at -80 degrees C. The post-preparation stability of spiked samples was more than 24 hours after preparation. The cartridge can be used two times providing a deviation of less than 4%. This method has adequate sensitivity, specificity, accuracy and precision to measure azithromycin in human plasma and is free from interference from the plasma matrix. The validated method was to quantify azithromycin plasma concentrations in five healthy Thai volunteers after the administration of 500 mg azithromycin capsules.

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.

An alternative high-performance liquid chromatographic method for determination of clindamycin in plasma.

A simple, sensitive, selective and reproducible method based on a reversed-phase chromatography was developed for the determination of clindamycin in human plasma. Clindamycin was separated from the internal standard (phenobarbital) on a Luna C18 column (250 x 4.6 mm, 5 mm particle size: Phenomenex, USA), with retention times of 5.6 and 14.2 minutes, respectively. Ultraviolet detection was set at 210 nm. The mobile phase consisted of a solution of 0.02 M disodiumhydrogenphosphate (pH 2.8) and acetonitrile (76:24 v/v), running through the column at a flow rate of 1.0 ml/min. The chromatographic analysis was operated at 25 degrees C. Sample preparation (1 ml plasma) was done by a single step liquid-liquid extraction with water saturated ethylacetate. Calibration curves in plasma at concentrations of 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 microg/ml were all linear with correlation coefficients better than 0.999. The precision of the method based on within-day repeatability and reproducibility (day-to-day variation) was below 15% (% coefficient of variations: %CV). Good accuracy was observed for both the intra-day and inter-day assays, as indicated by the minimal deviation of mean values found with measured samples from that of the theoretical values (below +/- 15%). Limit of quantification was accepted as 0.07 microg using 1 ml plasma sample. The mean recovery for clindamycin and the internal standard were greater than 95%. The method was free from interference from fosmidomycin, including commonly used drugs, antimalarials and antihelminthics. The method appears to be robust and has been applied to a pharmacokinetic study of clindamycin in a patient with malaria following oral doses of clindamycin at 10 mg/kg body weight given twice daily for 7 days.

Correlação entre dose/concentração plasmática e avaliação de alterações hepáticas e renais em ratos Wistar tratados com o esquema ROM / Correlation between dose/plasma concentration and assessment of hepatic and renal changes in Wistar rats treated with the ROM scheme

A hanseníase, doença crônica, granulomatosa, infecto-contagiosa, transmitida pelo Mycobacterium leprae, ainda se mantém prevalente nos dias atuais, principalmente em países subdesenvolvidos e a sua forma paucibacilar com lesão única, vem sendo tratada através da administração de rifampicina (600mg), ofloxacina (400mg) e minociclina (100mg), em dose única (esquema ROM). Assim, o objetivo deste trabalho foi investigar a correlação dose/concentração plasmática versus alterações bioquímicas na administração da rifampicina, ofloxacina e minociclina a ratos machos Wistar, em regime de dose única em mono e politerapia. Concluímos que a rifampicina e a ofloxacina sofreram um aumento na concentração plasmática quando administrados em politerapia, enquanto que a minociclina sofreu uma redução, provavelmente por interferências na biotransformação e excreção. Constatamos através das análises bioquímicas que a rifampicina provavelmente é a responsável por alterações hepáticas e renais, e que as interações medicamentosas envolvendo o fármaco exigem estudos individualizados principalmente quando o fármaco é usado associado a ofloxacina e minociclina.

Modification of pharmacokinetics of cefotaxime in uranyl nitrate-induced renal damage in black bengal goats

Pharmacokinetics of cefotaxime (50mg/kg, i.m.) were studied in both healthy and kidney damaged female black Bengal goats. Uranyl nitrate (0.75mg/kg) was administered intravenously, once daily for five consecutive days to induce kidney damage. The pharmacokinetic variables were calculated in both cases. Kidney damage caused several changes in the determined variables. The Cmax and Cmin of cefotaxime observed at 0.50 and 5 h in normal goats were 24.91+/-1.51 and 1.22+/-0.07 microgram/ml, respectively, while the same in kidney damaged goats at 1 and 72 h were 75.00+/-0.45 and 3.10+/-0.09 microgram/ml, respectively. Renal damage condition significantly increased t1/2,ka (0.48+/-0.01 h), t1/2,ke (20.03+/-0.16 h), AUC (2440.10+/-24.26 microgram. h/ml) and significantly decreased Vdarea (0.59+/-0.007L/kg), Vss (0.58+/-0.007 L/kg) and ClB (0.02+/-0.008 L/kg/h) values of cefotaxime compared to normal goats.

Comparative chemotherapeutic efficacy of balhimycin, desgluco-balhimycin against experimental MSSA and MRSA infection in mice.

Balhimycin and desglucobalhimycin are glycopeptide antibiotics isolated from an Amycolatopsis spp during the search for novel antibacterials against MRSA from the natural product screening at the Research Centre of formerly Hoechst India Ltd. in Bombay, India. Both compounds show excellent in vitro activity against methicillin sensitive and resistant Staphylococcus aureus (MSSA, MRSA). Both compounds were also found to be active against a number of MRSA strain in the animal studies. The activities were comparable to that of the reference glycopeptides vancomycin and teicoplanin used in these studies. Teicoplanin displayed better in vivo efficacy against S. epidermidis 4929H and Streptococcus pyogenes A77 than either vancomycin or desgluco-balhimycin in the present study. Preliminary studies on pharmacokinetic and acute toxicity were done to get some idea at the early stage of the investigation about the promise of the compounds for development.

Concentration of some prophylactic antibiotic in blood, dentoalveolar blood and mandibular bone in impaction surgery

Surgical removal of impacted third molars might be followed by infection. To fight against such infection an adequate antibiotic concentration should be there at the local tissue before the operation. This study was conducted to identify the level of single oral dose of prophylactic antibiotic in antecuhital serum, dentoalveolar serum and mandibular bone in impaction surgery. This study included 200 patients. divided into five groups each comprised forty patients and each group received single oral dose of one antibiotic under investigation [azithromycin. clindamycin. doxycycline. erythromycin, and penicillin-V]. Each group was further subdivided into eight subgroups comprising 5 patients according to the proposed time intervals. Antibiotics were taken 30. 60, 90. 120. 150. 180. 210, and 240 minutes before the operation according to the tested subgroup. Samples of blood. dentoalveolar blood and mandibular bone were taken at the planed time intervals. The concentrations of antibiotic in these samples were assayed in vitro by the agar diffusion [cup plate] method. The result showed that penicillin-V showed the highest mean peak serum concentration followed by doxycycline and clindamycin. However. all antibiotics gave measurable level exceeding the NBC of the tested bacterial isolates. Doxycycline showed the highest concentration ratio [bone/serum]. followed by penicillin-V, clindamycin and erythromycin. Up to four hours [240 minutes] no measurable level of azithromycin concentration could be attained in bone, so a further study at a longer time period [more than 12 hours] may be indicated. The suggested time for prophylactic use of the tested antibiotic should he two hours before the operation for clindamycin [300 mg]. one and half hour before the operation for erythromycin [500 mg]. three hours before the operation for doxycycline [200mg.] and half an hour before the operation for penicillin [937.5m2]