Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial).

BACKGROUND: Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM. METHODS: An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment.  DISCUSSION: Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM. TRIAL REGISTRATION: Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314 ). CLINICALTRIALS: gov NCT05917340. Registered on 6 August 2023 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT05917340 ). PROTOCOL VERSION: Version 1.3 dated 12 July 2023.

Nanocrystalline cellulose as a reinforcing agent for poly (vinyl alcohol)/ gellan-gum-based composite film for moxifloxacin ocular delivery.

Nanocrystalline cellulose (NCC) is a star material in drug delivery applications due to its good biocompatibility, large specific surface area, high tensile strength (TS), and high hydrophilicity. Poly(Vinyl Alcohol)/Gellan-gum-based innovative composite film has been prepared using nanocrystalline cellulose (PVA/GG/NCC) as a strengthening agent for ocular delivery of moxifloxacin (MOX) via solvent casting method. Impedance analysis was studied using the capacitive sensing technique for examining new capacitance nature of the nanocomposite MOX film. Antimicrobial properties of films were evaluated using Pseudomonas aeruginosa and Staphylococcus aureus as gram-negative and gram-positive bacteria respectively by disc diffusion technique. XRD revealed the characteristic peak of NCC and the amorphous form of the drug. Sustained in vitro release and enhanced corneal permeation of drug were noticed in the presence of NCC. Polymer matrix enhanced the mechanical properties (tensile strength 22.05 to 28.41 MPa) and impedance behavior (resistance 59.23 to 213.23 Ω) in the film due to the presence of NCC rather than its absence (16.78 MPa and 39.03â€¯Ω respectively). Occurrence of NCC brought about good antimicrobial behavior (both gram-positive and gram-negative) of the film. NCC incorporated poly(vinyl alcohol)/gellan-gum-based composite film exhibited increased mechanical properties and impedance behavior for improved ocular delivery of moxifloxacin.

Azithromycin and moxifloxacin resistance determinants in Mycoplasma genitalium in Lleida, Spain.

OBJECTIVE: Mycoplasma genitalium (MG) is a microorganism related to sexually transmitted infections. Antibiotic resistance of MG leads to an increase in treatment failure rates and the persistence of the infection. The aim of this study was to describe the most frequent mutations associated with azithromycin and moxifloxacin resistance in our geographical area. METHODS: A prospective study from May 2019 to May 2023 was performed. MG-positive samples were collected. Real-time PCRs (AllplexTM MG-AziR Assay and AllplexTM MG-MoxiR Assay, Seegene) were performed in MG positive samples to detect mutations in 23S rRNA V domain and parC gene. RESULTS: A 37.1% of samples presented resistance determinants to azithromycin and the most common mutation detected was A2059G (57.9%). Resistance to moxifloxacin was studied in 72 azithromycin-resistant samples and 36.1% showed mutations, being G248T the most prevalent (73.1%). CONCLUSIONS: The resistance to different lines of treat ment suggests the need for a targeted therapy and the performing of a test of cure afterwards.

Differences in nature killer cell response and interference with mitochondrial DNA induced apoptosis in moxifloxacin environment.

OBJECTIVES: As antibiotics become more prevalent, accuracy and safety are critical. Moxifloxacin (MXF) have been reported to have immunomodulatory effects on a variety of immune cells and even anti-proliferative and pro-apoptotic effects, but the mechanism of action is not fully clear. METHODS: Peripheral blood mononuclear cells (PBMC) from experimental groups of healthy adults (n = 3) were treated with MXF (10ug/ml) in vitro for 24 h. Single-cell sequencing was performed to investigate differences in the response of each immune cell to MXF. Flow cytometry determined differential gene expression in subsets of most damaged NK cells. Pseudo-time analysis identified drivers that influence MXF-stimulated cell differentiation. Detection of mitochondrial DNA and its involvement in the mitochondrial respiratory chain pathway clarifies the origin of MXF-induced stress injury. RESULTS: Moxifloxacin-environmental NK cells are markedly reduced: a new subset of NK cells emerges, and immediate-early-response genes in this subset indicate the presence of an early activation response. The inhibitory receptor-dominant subset shows enhanced activation, leading to increased expression of cytokines and chemokines. The near-mature subset showed greater cytotoxicity and the most pronounced cellular damage. CD56bright cells responded by antagonizing the regulation of activation and inhibitory signals, demonstrating a strong cleavage capacity. The severe depletion of mitochondrial genes was focused on apoptosis induced by the mitochondrial respiratory chain complex. CONCLUSION: NK cells exhibit heightened sensitivity to the MXF environment. Different NK subsets upregulate the expression of cytokines and chemokines through different activation pathways. Concurrently, MXF induces impairment of the mitochondrial oxidative phosphorylation system, culminating in apoptosis.

Successful maintenance treatment of disseminated nocardiosis with cerebral abscess in a severely immunocompromised patient allergic to trimethoprim-sulfamethoxazole using moxifloxacin and high-dose minocycline: A case report.

Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although trimethoprim-sulfamethoxazole (TMP/SMX) remains the cornerstone of nocardiosis treatment, optimal alternative therapies for patients intolerant to TMP/SMX are not well-established. Herein, we report a case of disseminated nocardiosis with bacteremia and multiple lesions in the lungs and brain caused by Nocardia farcinica, in a 60-year-old man who had previously undergone allogeneic HSCT and was receiving immunosuppressants for severe chronic graft-versus-host disease. The patient received atovaquone for the prophylaxis of Pneumocystis pneumonia because of a previous serious allergic reaction to TMP/SMX. The patient was initially treated with imipenem/cilastatin and amikacin, which were later switched to ceftriaxone and amikacin based on the results of antimicrobial susceptibility testing. After switching to oral levofloxacin and a standard dose of minocycline, the patient experienced a single recurrence of brain abscesses. However, after switching to oral moxifloxacin and high-dose minocycline, the patient did not experience any relapses during the subsequent two years and seven months of treatment. In treating nocardiosis with brain abscesses, it is crucial to select oral antibiotics based on the antimicrobial susceptibility test results and pharmacokinetics, especially when TMP/SMX is contraindicated. A combination of oral moxifloxacin and high-dose minocycline could be a promising alternative therapy.

Evaluation of critical parameters in the hollow-fibre system for tuberculosis: A case study of moxifloxacin.

AIMS: The hollow­fibre system for tuberculosis (HFS­TB) is a preclinical model qualified by the European Medicines Agency to underpin the anti­TB drug development process. It can mimic in vivo pharmacokinetic (PK)­pharmacodynamic (PD) attributes of selected antimicrobials, which could feed into in silico models to inform the design of clinical trials. However, historical data and published protocols are insufficient and omit key information to allow experiments to be reproducible. Therefore, in this work, we aim to optimize and standardize various HFS­TB operational procedures. METHODS: First, we characterized bacterial growth dynamics with different types of hollow­fibre cartridges, Mycobacterium tuberculosis strains and media. Second, we mimicked a moxifloxacin PK profile within hollow­fibre cartridges, in order to check drug­fibres compatibility. Lastly, we mimicked the moxifloxacin total plasma PK profile in human after once daily oral dose of 400 mg to assess PK­PD after different sampling methods, strains, cartridge size and bacterial adaptation periods before drug infusion into the system. RESULTS: We found that final bacterial load inside the HFS­TB was contingent on the studied variables. Besides, we demonstrated that drug­fibres compatibility tests are critical preliminary HFS­TB assays, which need to be properly reported. Lastly, we uncovered that the sampling method and bacterial adaptation period before drug infusion significantly impact actual experimental conclusions. CONCLUSION: Our data contribute to the necessary standardization of HFS­TB experiments, draw attention to multiple aspects of this preclinical model that should be considered when reporting novel results and warn about critical parameters in the HFS­TB currently overlooked.

Topical Antibiotic Therapy in the Ocular Environment: The Benefits of Using Moxifloxacin Eyedrops.

Moxifloxacin is a fourth-generation fluoroquinolone antibiotic available for ophthalmic use. It inhibits two enzymes involved in bacterial DNA synthesis, covering Gram-positive and Gram-negative pathogens. This spectrum allows for the formulation of self-preserving bottle solutions, while its interesting pharmacological profile is distinguished by efficacy at low tissue concentrations and by an infrequent dose regimen due to its long duration on ocular tissues. This enhances patient compliance, promoting its use in children. The human eye hosts several microorganisms; this collection is called the ocular microbiota, which protects the ocular surface, assuring homeostasis. When choosing an antibiotic, it is appropriate to consider its influence on microbiota. A short dose regimen is preferred to minimize the impact of the drug. Moxifloxacin eyedrops represent an effective and safe tool to manage and prevent ocular infections. As healthcare providers face the complexity of the ocular microbiota and microbial resistance daily, the informed use of moxifloxacin is necessary to preserve its efficacy in the future. In this regard, it is well known that moxifloxacin has a lower capacity to induce resistance (an optimal WPC and MPC) compared to other quinolones, but much still needs to be explored regarding the impact that fluoroquinolones could have on the ocular microbiota.

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The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

Bacteria-Targeting Nanoparticles with ROS-Responsive Antibiotic Release to Eradicate Biofilms and Drug-Resistant Bacteria in Endophthalmitis.

Background: Bacterial endophthalmitis is an acute progressive visual threatening disease and one of the most important causes of blindness worldwide. Current treatments are unsatisfactory due to the emergence of drug-resistant bacteria and the formation of biofilm. Purpose: The aim of our research was to construct a novel nano-delivery system with better antimicrobial and antibiofilm effects. Methods: This study developed a novel antibiotic nanoparticle delivery system (MXF@UiO-UBI-PEGTK), which is composed of (i) moxifloxacin (MXF)-loaded UiO-66 nanoparticle as the core, (ii) bacteria-targeting peptide ubiquicidin (UBI29-41) immobilized on UiO-66, and (iii) ROS-responsive poly (ethylene glycol)-thioketal (PEG-TK) as the surface shell. Then the important properties of the newly developed delivery system, including biocompatibility, toxicity, release percentage, thermal stability, ability of targeting bacteria, and synergistic antibacterial effects on bacterial biofilms and endophthalmitis, were evaluated. Results: In vitro, MXF@UiO-UBI-PEGTK exhibited significant antibiotic effects including the excellent antibiofilm property against Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus at high levels of ROS. Moreover, MXF@UiO-UBI-PEGTK demonstrated outstanding efficacy in treating bacterial endophthalmitis in vivo. Conclusion: This novel nanoparticle delivery system with ROS-responsive and bacteria-targeted properties promotes the precise and effective release of drugs and has significant potential for clinical application of treating bacterial endophthalmitis.

Predictors of Successful First-Line Helicobacter pylori Eradication with Fluoroquinolones in Pakistan: A Prospective Exploration of Demographic and Clinical Factors.

Growing antibiotic resistance complicates H. pylori eradication, posing a public health challenge. Inconclusive research on sociodemographic and clinical factors emphasizes the necessity for further investigations. Hence, this study aims to evaluate the correlation between demographic and clinical factors and the success rates of H. pylori eradication. A group of 162 H. pylori-positive patients were allocated randomly to receive either a ten-day moxifloxacin-based triple therapy or a levofloxacin-based sequential therapy. Eradication success was determined through the stool antigen test. Logistic regression analysis was utilized to figure out potential factors that contribute to H. pylori eradication success. Significantly higher H. pylori eradication rates were observed in the middle age group (COR: 3.671, p = 0.007), among females (p = 0.035), those with BMI ≥ 25 (COR: 2.011, p = 0.045), and non-smokers (COR: 2.718, p = 0.018). In multivariate analysis, age and smoking emerged as significant predictors (p < 0.05). Patients with comorbidities, excluding diabetes and hypertension (COR: 4.432, p = 0.019), dyspepsia (COR: 0.178, p < 0.001), and moxifloxacin triple therapy (COR: 0.194, p = 0.000), exhibited higher chances of eradication (p < 0.05). Further research is vital for tailored approaches to enhance eradication success.

Triple combination dry powder formulation of pretomanid, moxifloxacin, and pyrazinamide for treatment of multidrug-resistant tuberculosis.

Both latent and multidrug-resistant tuberculosis (TB) have been causing significant concern worldwide. A novel drug, pretomanid (PA-824), has shown a potent bactericidal effect against both active and latent forms of Mycobacterium tuberculosis (MTb) and a synergistic effect when combined with pyrazinamide and moxifloxacin. This study aimed to develop triple combination spray dried inhalable formulations composed of antitubercular drugs, pretomanid, moxifloxacin, and pyrazinamide (1:2:8 w/w/w), alone (PaMP) and in combination with an aerosolization enhancer, L-leucine (20 % w/w, PaMPL). The formulation PaMPL consisted of hollow, spherical, dimpled particles (<5 µm) and showed good aerosolization behaviour with a fine particle fraction of 70 %. Solid-state characterization of formulations with and without L-leucine confirmed the amorphous nature of moxifloxacin and pretomanid and the crystalline nature of pyrazinamide with polymorphic transformation after the spray drying process. Further, the X-ray photoelectron spectroscopic analysis revealed the predominant surface composition of L-leucine on PaMPL dry powder particles. The dose-response cytotoxicity results showed pyrazinamide and moxifloxacin were non-toxic in both A549 and Calu-3 cell lines up to 150 µg/mL. However, the cell viability gradually decreased to 50 % when the pretomanid concentration increased to 150 µg/mL. The in vitro efficacy studies demonstrated that the triple combination formulation had more prominent antibacterial activity with a minimum inhibitory concentration (MIC) of 1 µg/mL against the MTb H37Rv strain as compared to individual drugs. In conclusion, the triple combination of pretomanid, moxifloxacin, and pyrazinamide as an inhalable dry powder formulation will potentially improve treatment efficacy with fewer systemic side effects in patients suffering from latent and multidrug-resistant TB.

Cationized gelatin-sodium alginate polyelectrolyte nanoparticles encapsulating moxifloxacin as an eye drop to treat bacterial keratitis.

A mucoadhesive polyelectrolyte complex (PEC) nanoparticles were developed for ocular moxifloxacin (Mox) delivery in Bacterial Keratitis (BK). Moxifloxacin-loaded G/CG-Alg NPs were prepared by an amalgamation of cationic polymers (gelatin (G)/cationized gelatin (CG)), and anionic polymer (sodium alginate (Alg)) along with Mox respectively. Mox@CG-Alg NPs were characterized for physicochemical parameters such as particle size (DLS technique), morphology (SEM analysis), DSC, XRD, encapsulation efficiency, drug loading, mucoadhesive study (by texture analyzer), mucin turbidity, and viscosity assessment. The NPs uptake and toxicity of the formulation were analyzed in the Human Corneal Epithelial (HCE) cell line and an ocular irritation study was performed on the HET-CAM. The results indicated that the CG-Alg NPs, with optimal size (217.2 ± 4 nm) and polydispersity (0.22 ± 0.05), have shown high cellular uptake in monolayer and spheroids of HCE. The drug-loaded formulation displayed mucoadhesiveness, trans-corneal permeation, and sustained the release of the Mox. The anti-bacterial efficacy studied on planktonic bacteria/biofilms of P. aeruginosa and S. aureus (in vitro) indicated that the Mox@CG-Alg NPs displayed low MIC, higher zone of bacterial growth inhibition, and cell death compared to free Mox. A significant reduction of bacterial load was observed in the BK-induced mouse model.

T-wave morphology abnormalities in the STREAM stage 1 trial.

BACKGROUND: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation. RESEARCH DESIGN AND METHODS: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate). RESULTS: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25). CONCLUSIONS: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.

Efficacy and Influencing Factors of Sangju Cough Mixture in the Adjuvant Treatment of Adult Patients with Mycoplasma pneumoniae Infection: A Retrospective Study.

Purpose: Sangju-Yin, supplemented with some drugs, has frequently demonstrated therapeutic efficacy against colds, albeit its effect on Mycoplasma pneumoniae (MP) infection remains unknown. Therefore, we aimed to elucidate the treatment efficacy and influencing factors of a Sangju cough mixture on MP infection in adults. Patients and Methods: Between January 2021 and December 2022, 150 adult patients with MP infection at the Lishui Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Traditional Chinese Medicine were assigned to the treatment (administered Sangju cough mixture and moxifloxacin tablets) or the control (administered moxifloxacin tablets) groups. Results: When compared with the control group, the treatment group exhibited significantly improved traditional Chinese medicine syndrome scores, increased CD4+ T cell levels, and decreased CD8+ T cell levels (all P < 0.05). After 7 days of treatment, the negative conversion rate of the MP-specific immunoglobulin M (MP-IgM) antibody of the treatment group was not significantly different from that of the control group (P > 0.05); however, after 14 days of treatment, the rate was significantly higher in the treatment group (P < 0.05). The univariate regression analysis revealed that combined chronic respiratory disease, failure to take Sangju cough mixture, combined pneumonia, Nutritional Risk Screening 2002 (NRS 2002) score of at least 3 points, and age were associated with the negative conversion of the MP-IgM antibody (all P < 0.05). Nevertheless, the multivariate regression model revealed that the NRS 2002 score of at least 3 points was not an independent risk factor (P > 0.05). Conclusion: Sangju cough mixture can improve symptoms, accelerate the negative conversion time of MP-IgM antibody, and promote rehabilitation of the patients.

Targeted repression of topA by CRISPRi reveals a critical function for balanced DNA topoisomerase I activity in the Chlamydia trachomatis developmental cycle.

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form to an infectious form. Consistent with this, expression of late developmental genes of C. trachomatis was downregulated, while early genes maintained their expression. Importantly, the developmental defect associated with topA knockdown was rescued by overexpressing topA at an appropriate degree and time, directly linking the growth patterns to the levels of topA expression. Interestingly, topA knockdown had effects on DNA gyrase expression, indicating a potential compensatory mechanism for survival to offset TopA deficiency. C. trachomatis with topA knocked down displayed hypersensitivity to moxifloxacin that targets DNA gyrase in comparison with the wild type. These data underscore the requirement of integrated topoisomerase actions to support the essential developmental and transcriptional processes of C. trachomatis.IMPORTANCEWe used genetic and chemical tools to demonstrate the relationship of topoisomerase activities and their obligatory role for the chlamydial developmental cycle. Successfully targeting the essential gene topA with a CRISPRi approach, using dCas12, in C. trachomatis indicates that this method will facilitate the characterization of the essential genome. These findings have an important impact on our understanding of the mechanisms by which well-balanced topoisomerase functions in adaptation of C. trachomatis to unfavorable growth conditions imposed by antibiotics.

Ocular bioanalysis of moxifloxacin and ketorolac tromethamine in rabbit lacrimal matrix using liquid chromatography-tandem mass spectrometry.

Aim: The fixed-dose combination of moxifloxacin (MOXI) and ketorolac tromethamine (KTR) is widely used for the treatment of bacterial keratitis. Thus, a new LC-MS/MS method was developed to determine MOXI and KTR in lacrimal fluid. Methods: Bioanalysis was performed using a Shimadzu 8050 LC-MS/MS in electrospray ionization-positive mode and the method was validated per US FDA guidelines. Isocratic separation was performed with a Waters Symmetry C18 column using methanol and 0.1% formic acid containing deionized water (85:15, v/v). Results & conclusion: An easy, quick and selective method was established and applied to assess the ocular pharmacokinetic profile of a commercially available formulation containing MOXI and KTR. Based on the pharmacokinetic data, this work describes pharmacokinetics-based dosage regimen calculations and their clinical significance.

Effect of Dexketoprofen on the Disposition Kinetics of Moxifloxacin in Plasma and Lung in Male and Female Rats.

BACKGROUND: The simultaneous use of NSAIDs and antibiotics is recommended for bacterial dis-eases in human and veterinary medicine. Moxifloxacin (MFX) and dexketoprofen (DEX) can be used simul-taneously in bacterial infections. However, there are no studies on how the simultaneous use of DEX affects the pharmacokinetics of MFX in rats. OBJECTIVES: The aim of this study was to determine the effect of DEX on plasma and lung pharmacokinetics of MFX in male and female rats. METHODS: A total of 132 rats were randomly divided into 2 groups: MFX (n=66, 33 males/33 females) and MFX+DEX (n=66, 33 females/33 males). MFX at a dose of 20 mg/kg and DEX at a dose of 25 mg/kg were administered intraperitoneally. Plasma and lung concentrations of MFX were determined using the high-performance liquid chromatography-UV and pharmacokinetic parameters were evaluated by non-compartmental analysis. RESULTS: Simultaneous administration of DEX increased the plasma and lung area under the curve from 0 to 8 h (AUC0-8) and peak concentration (Cmax) of MFX in rats, while it significantly decreased the total body clearance (CL/F). When female and male rats were compared, significant differences were detected in AUC0-8, Cmax, CL/F and volume of distribution. The AUC0-8lung/AUC0-8plasma ratios of MFX were calculated as 1.68 and 1.65 in female rats and 5.15 and 4.90 in male rats after single and combined use, respectively. CONCLUSION: MFX was highly transferred to the lung tissue and this passage was remarkably higher in male rats. However, DEX administration increased the plasma concentration of MFX in both male and female rats but did not change its passage to the lung. However, there is a need for a more detailed investigation of the difference in the pharmacokinetics of MFX in male and female rats.

Eco-friendly novel deconvoluted synchronous spectrofluorimetric approach for the determination of favipiravir, levodropropizine and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in laboratory prepared mixtures and spiked human plasma.

In this work, a green, fast, and simple synchronous spectrofluorimetric approach has been developed to simultaneously determine favipiravir, levodropropizine, and moxifloxacin hydrochloride as co-administered medications for COVID-19 treatment in pure form and spiked human plasma. The synchronous fluorescence spectroscopy technique to analyze the studied drugs at Δλ = 110 nm enabled the determination of levodropropizine at 360 nm. Then, applying Fourier Self-Deconvolution to each spectra to measure favipiravir and moxifloxacin hydrochloride at peak amplitudes of 431 nm and 479 nm, respectively, without any interference. Favipiravir, levodropropizine, and moxifloxacin hydrochloride could be sensitively determined using the described approach over concentration ranges of 20-300 ng/mL, 10-600 ng/mL, and 50-500 ng/mL, respectively. The method's validation was carried out effectively in accordance with guidelines recommended by the ICH. Finally, the Eco-scale and Green Analytical Procedure Index (GAPI) techniques have been used to evaluate the greenness of the proposed method.

Toward Digital Twin Technology for Precision Pharmacology.

The authors demonstrate the feasibility of technological innovation for personalized medicine in the context of drug-induced arrhythmia. The authors use atomistic-scale structural models to predict rates of drug interaction with ion channels and make predictions of their effects in digital twins of induced pluripotent stem cell-derived cardiac myocytes. The authors construct a simplified multilayer, 1-dimensional ring model with sufficient path length to enable the prediction of arrhythmogenic dispersion of repolarization. Finally, the authors validate the computational pipeline prediction of drug effects with data and quantify drug-induced propensity to repolarization abnormalities in cardiac tissue. The technology is high throughput, computationally efficient, and low cost toward personalized pharmacologic prediction.