Novel COVID-19 biomarkers identified through multi-omics data analysis: N-acetyl-4-O-acetylneuraminic acid, N-acetyl-L-alanine, N-acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate.

This study aims to apply machine learning models to identify new biomarkers associated with the early diagnosis and prognosis of SARS-CoV-2 infection.Plasma and serum samples from COVID-19 patients (mild, moderate, and severe), patients with other pneumonia (but with negative COVID-19 RT-PCR), and healthy volunteers (control) from hospitals in four different countries (China, Spain, France, and Italy) were analyzed by GC-MS, LC-MS, and NMR. Machine learning models (PCA and PLS-DA) were developed to predict the diagnosis and prognosis of COVID-19 and identify biomarkers associated with these outcomes.A total of 1410 patient samples were analyzed. The PLS-DA model presented a diagnostic and prognostic accuracy of around 95% of all analyzed data. A total of 23 biomarkers (e.g., spermidine, taurine, L-aspartic, L-glutamic, L-phenylalanine and xanthine, ornithine, and ribothimidine) have been identified as being associated with the diagnosis and prognosis of COVID-19. Additionally, we also identified for the first time five new biomarkers (N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate) that are also associated with the severity and diagnosis of COVID-19. These five new biomarkers were elevated in severe COVID-19 patients compared to patients with mild disease or healthy volunteers.The PLS-DA model was able to predict the diagnosis and prognosis of COVID-19 around 95%. Additionally, our investigation pinpointed five novel potential biomarkers linked to the diagnosis and prognosis of COVID-19: N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate. These biomarkers exhibited heightened levels in severe COVID-19 patients compared to those with mild COVID-19 or healthy volunteers.

Pharmacokinetics of oral ciprofloxacin in adult patients: A scoping review.

AIMS: To map the literature on oral ciprofloxacin's pharmacokinetics and its implications for dose adjustments in specific populations. METHODS: A scoping review was performed according to the Cochrane Collaboration and JBI and reported following the PRISMA-ScR. Systematic searches on electronic databases were conducted to integrate the current evidence on ciprofloxacin's pharmacokinetics. The quality of the included studies was assessed using ClinPK's checklist. RESULTS: The search yielded 55 relevant studies. Within the traditional pharmacokinetics studies (n = 46), 86 profiles were examined (72 involving healthy patients and 14 with various clinical conditions). Oral ciprofloxacin's pharmacokinetics were influenced by covariates such as drug interactions (ferrous ions, calcium carbonate, diclofenac and itraconazole), food interactions (calcium-rich foods), elderly populations and renal impairment. Notably, variability in pharmacokinetic parameters existed among subjects, regardless of their health status, underscoring the need for comprehensive population descriptions. Population pharmacokinetic studies (n = 9) identified significant covariates for hospitalized patients, such as creatinine clearance, plasma bicarbonate, estimated glomerular filtration rate, renal replacement therapy, age, sex, total bilirubin, fat-free mass, dietary factors in renal disease, rifampicin for clearance models and body weight for volume of distribution models. Most pharmacokinetic/pharmacodynamic assessments concluded that 1200 mg/day provides a high probability of target attainment for bacteria with minimum inhibitory concentration <0.5 mg L-1 , aiming for an area under the curve for 24 h/minimum inhibitory concentration >125 h. CONCLUSIONS: This study offers a comprehensive overview regarding oral ciprofloxacin's pharmacokinetics across various health conditions. It highlights the complexities of ciprofloxacin's pharmacokinetics, emphasizing the importance of considering multiple factors in dose adjustments.

Advanced formulations and nanotechnology-based approaches for pulmonary delivery of sildenafil: A scoping review.

Oral sildenafil (SDF) is used to treat pulmonary arterial hypertension (PAH), and its bioavailability is approximately 40%. Several formulations of nano and microparticles (for pulmonary delivery) are being developed because it is possible to improve characteristics such as release time, bioavailability, dose, frequency, and even directly target the drug to the lungs. This review summarizes the latest SDF drug delivery systems for PAH and explains challenges related to the development, the preclinical, and the clinical studies. A scoping review was conducted by searching electronic databases including PubMed, Scopus, and Web of Science to identify studies published between 2001 and 2021. From 300 articles found, 31 met the inclusion criteria. This review identified colloidal formulations such as polymeric, lipid, and metal-organic framework nanoparticles. Strategies were determined to reach the deep airways such as polymeric microparticles, large porous microparticles, nanocomposites, and nano in microparticles. Finally, aspects related to toxicological, pharmacokinetics, and gaps in information for potential use in humans were discussed. SDF formulations are significant candidates for the treatment of PAH by inhalation. In summation, future preclinical studies are still required in large animals, as there is no particular formulation yet submitted to clinical studies.

Comparator product issues for biowaiver implementation: the case of Fluconazole

The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria

Pharmaceutical applications of starch nanoparticles: A scoping review.

Starch nanoparticles (SNPs) have been applied to different areas of material sciences, especially in pharmaceuticals due to their characteristics such as small particle size, high surface ratio-volume, and biological compatibility. However, in pharmaceutical sciences, there are no records of a scoping review that had extensively mapped all available information about SNPs. A scoping review was performed here by searching electronic databases (Pubmed and Science Direct) to identify studies published previous to June 2020. From 699 total records, 37 matched the criteria for inclusion. The findings showed that SNPs have been used, not only for the development of different active pharmaceutical ingredient delivery systems, but also as an enzyme inhibitor, adsorption, and DNA precipitation agent. In conclusion, by combining different starch sources and methods SNPs show a remarkable diversity in pharmaceutical applications. Future studies should explore SNPs safety and provide information about variables that may affect important properties for this kind of application.