Population Pharmacokinetic Modeling of Free Plasma and Free Brain Concentrations of Ceftaroline in Healthy and Methicillin-Resistant Staphylococcus aureus-Infected Wistar Rats.

A population pharmacokinetic model was developed to describe alterations in ceftaroline brain disposition caused by meningitis in healthy and methicillin-resistant Staphylococcus aureus (MRSA)-infected rats. Blood and brain microdialysate samples were obtained after a single bolus dose of ceftaroline fosamil (20 mg/kg) administered intravenously. Plasma data were modeled as one compartment, and brain data were added to the model as a second compartment, with bidirectional drug transport between plasma and brain (Qin and Qout). The cardiac output (CO) of the animals showed a significant correlation with the relative recovery (RR) of plasma microdialysis probes, with animals with greater CO presenting lower RR values. The Qin was approximately 60% higher in infected animals, leading to greater brain exposure to ceftaroline. Ceftaroline brain penetration was influenced by MRSA infection, increasing from 17% (Qin/Qout) in healthy animals to 27% in infected animals. Simulations of a 2-h intravenous infusion of 50 mg/kg every 8 h achieved >90% probability of target attainment (PTA) in plasma and brain for the modal MRSA MIC (0.25 mg/L), suggesting that the drug should be considered an option for treating central nervous system infections.

Development and validation of an LC-MS/MS method to quantify ceftaroline in microdialysate samples from plasma and brain: Application to a preclinical pharmacokinetic investigation.

A bioanalytical LC-MS/MS method was developed and validated to determine ceftaroline in microdialysate samples from plasma and brain. Ceftaroline was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 5 mM of ammonium formate and acid formic 0.1%, eluted as gradient. Ceftaroline was monitored using electrospray ionization operating on positive mode (ESI+) monitoring the transition 604.89 > 209.3 m/z. The method showed linearity in the concentration range of 0.5-500 ng/mL for brain microdialysate and 0.5-2500 ng/mL for plasma microdialysate with coefficients of determination ≥0.997. The inter-and intra-day precision, the accuracy, and the stability of the drug in different conditions were in accordance with the acceptable limits determined by international guidelines. Plasma pharmacokinetics and brain distribution of the drug were carried out after intravenous administration of 20 mg/kg of ceftaroline to male Wistar rats. The estimated geometric mean (geometric coefficient of variation) area under the curve (AUC0-∞) was 4.68 (45.8%) mg·h/L and 1.20 (54.2%) mg·h/L for plasma and brain, respectively, resulting in a brain exposure of about 33% (AUCfree brain/AUCfree plasma). The results indicate that ceftaroline presents good penetration in the brain when considering free plasma and free brain concentrations.

Residues of Veterinary Drugs in Animal Products Commercialized in the Border Region of Brazil, Argentina, and Uruguay.

ABSTRACT: The traffic in international animal products can become a public health hazard when legal import sanitary procedures are not followed. In Brazil, due to its extensive border area, the importation of animal products is a common practice in many areas, especially in Rio Grande do Sul, a state that borders Argentina and Uruguay. The objective of this study was to evaluate the presence of veterinary drug residues (antibiotics and antiparasitics) in animal products consumed in Rio Grande do Sul. The presence of residues of veterinary antibiotics and antiparasitics was assessed in 189 meat (beef, pork, and chicken), processed dairy, and meat product samples bought in Argentina (n = 90) and Uruguay (n = 99). Residues of these veterinary drugs were detected in 50 (26.45%) of the samples; 28 samples (14.81%) had antibiotic residues, and 22 samples (11.64%) had antiparasitic residues. Of the 50 positive samples, 40% (15 from Argentina and 5 from Uruguay) had residues above the maximum residue limits (MRLs). Of these 20 samples, 12 had antiparasitic residues above the MRLs (11 beef samples had ivermectin and 1 pork sample had ivermectin and doramectin) and 8 had antibiotic residues above the MRLs (2 pork and 2 sausage samples had doxycycline, 2 cheese samples had doxycycline and chlortetracycline, 1 poultry meat sample had chloramphenicol, and 1 cheese sample had monensin). Because of the potential toxic effects on humans and the potential for pathogens to develop antibiotic resistance, the presence of these residues above the MRLs is a potential risk to public health. The negative impact of consumption of imported animal products can be reduced by implementation of an effective surveillance system and educational campaigns for the general population.

Microbiological and physicochemical characteristics of buffalo milk used for dairy products in southern Brazil.

In Brazil, the buffalo milk market has been growing. However, identity and quality standards have not been established for this raw material, nor have proper distinctions between buffalo milk and bovine milk been defined. Currently, the State of Rio Grande do Sul (RS) has only three producers that supply raw material for officially marketed derivatives. The aim of this study was to determine the identity and quality standards of raw buffalo milk in this region. Samples were obtained biweekly from three farm cooling tanks between June 2017 and August 2018, to reach a total of 69 samples. The averages for the results of the physicochemical parameters fat, protein, lactose, total solids, SNF (solids-not-fat), calcium, density, FP, acidity and SCC were 5.5 g/100 g, 4.06 g/100 g, 5.07 g/100 g, 15.5 g/100 g, 9.96 g/100 g, 0.161 g/100 g, 1.034 g/ml, -0.527°C, 16°D and 95 × 103 cells/ml, respectively. With reference to the microbiological parameters, the mean of the Standard Plate Count (SPC) and thermotolerant coliforms were 9,0 × 104 CFU/ml and 1.6 × 102 MPN/ml, respectively. Regarding coagulase-positive staphylococci, 36 samples tested positive (52% of total). Neither Salmonella spp. nor Listeria monocytogenes, nor antibiotic or antiparasitic residues were detected in any sample. In conclusion, the buffalo milk used as raw material for dairy products in southern Brazil demonstrated satisfactory physicochemical and microbiological characteristics, in accordance with recent scientific literature.

Retention of vitamin A after goat milk processing into cheese: a nutritional strategy.

The deficiency in micronutrients is a public health problem, principally in lower-middle-income countries. Vitamin A (VA) is considered a micronutrient fundamental to the maintenance and development of different tissues in the organism. Therefore, it is an essential micronutrient in the human diet. In these terms, goat milk is the leading food consumed to provide nutritional support in innumerous lower-middle-income countries. Here our work aimed to produce goat cheese studying strategies to promote the retention of VA. Our experiment design also explores the use of the salting process to evaluate the levels of VA retention. The level of VA in goat cheese was determined using LC-MS/MS analysis. Additionally, the redox status of the goat cheese in terms of lipid peroxidation and protein oxidation was determined. The texture analysis was also evaluated to verify if the redox status and salting process influence the texture profile. The results showed that the salting process during goat cheese production improves the retention of VA in goat cheese. Moreover, the salting process also is related to alterations in the status redox of the goat cheese and texture parameters. Therefore, our results show that goat cheese production can be an alternative to produced dairy derivates with recognized concentrations of VA for human nutrition.

The effect of breed, sex, and drug concentration on the pharmacokinetic profile of ivermectin in cattle.

Ivermectin (IVM) is one of the most widely used antiparasitic drugs worldwide and has become the drug of choice for anthelmintic and tick treatment in beef cattle production. It is known that pharmacokinetic parameters are fundamental to the rational use of a drug and food safety and these parameters are influenced by different factors. The aim of this study was to evaluate the pharmacokinetic profile of IVM in Bos indicus, Bos taurus, and crossbreed cattle (B. indicus × B. taurus) kept under same field conditions and the possible impacts of sex and IVM formulation (1% and 3.15%). It was observed that IVM concentration was significantly affected by breed. The plasma concentrations of IVM, AUC, Cmax , and t1/2ß were significantly higher in B. indicus compared to B. taurus. Crossbreed animals showed an intermediate profile between European and Indian cattle. No alteration in pharmacokinetics parameters was detected when comparing different gender. Concerning the pharmacokinetic data of IVM formulation, it was verified that Tmax , AUC, and t1/2ß were higher in 3.15% IVM animals than those from 1% IVM formulation. The results clearly indicated that the IVM plasma concentrations in B. indicus were higher than that in B. taurus.