Efficacy and safety of intravenous and/or oral levonadifloxacin in the management of secondary bacterial pulmonary infections in COVID-19 patients: findings of a retrospective, real-world, multi-center study

Background: Owing to dysregulated immune response, secondary bacterial pulmonary infections involving both gram-positive and gram-negative pathogens are common in COVID-19 patients and are often associated with higher mortality. This is a first ever report on the safety and efficacy of levonadifloxacin in the treatment of secondary bacterial pulmonary infections in patients with COVID-19 pneumonia.Methods: This multi-center, retrospective, post-marketing and real-world study assessed the safety and efficacy of IV and/or oral levonadifloxacin in the treatment of bacterial infections encountered in COVID-19 patients. Data for 154 male/female patients above 18 years of age who received levonadifloxacin (injectable and/or oral) was collected from 44 participating sites. Study outcomes were the clinical and microbial success at the end of therapy. Safety was assessed based on clinical and laboratory adverse events.Results: Among the 154 patients assessed, 121 (78.6%) were males and 142 (92.2%) were hospitalized. Majority of the patients (119) received all-IV therapy while 11 patients were prescribed with IV followed by oral regimen. All-oral therapy was received by 24 patients. The most common co-morbid conditions were diabetes (19.6%) and hypertension (19.2%). Post-treatment with levonadifloxacin, clinical and microbial success rates were 96.8% and 97.0% respectively.Conclusions: Levonadifloxacin showed promising safety and efficacy when used as IV and/or oral therapy for the treatment of secondary bacterial pulmonary infections in COVID-19 patients. Clinically relevant features of levonadifloxacin such as availability of both IV and oral options, broad spectrum coverage and reassuring safety in patients with significant co-morbidities could help simplify the management.Trial registration no. CTRI/2020/09/028152 [Registered on: 30/09/2020]

Clinical pharmacokinetics and pharmacodynamics of vildagliptin 50 mg sustained release tablet formulation in healthy Indian males after single and multiple-dose

Background: Vildagliptin 50 mg once-daily is a clinically established anti-diabetic therapy in combination with a sulphonylurea and renally impaired patients. We developed sustained release (SR) vildagliptin 50 mg tablet formulation for prolongation of dipeptidyl peptidase-4 (DPP-4) inhibition coverage. The present study compares the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of investigational vildagliptin SR 50 mg tablet with Galvus® in healthy Indian adult males after single and multiple-dose administration.Methods: Each randomized, open-label, two-period, cross-over study enrolled 36 healthy Indian adult male subjects for the assessment of single and multiple-dose PK/PD profiles of SR 50 mg vildagliptin under fed condition. The plasma drug concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. PK parameters (Cmax (ng/ml), AUC0-18, AUC0-36, and AUC0-τ (ng.hr/ml), Tmax (hour), t1/2 (hour), Tmaxss (hour), Cτss (ng.hr/ml) were calculated using Phoenix® WinNonlin® software. The DPP-4 inhibition was determined in a fluorescence-based assay.Results: Vildagliptin SR tablet showed prolonged PK/PD characters compared to Galvus®. All PK parameters expressed as Mean±SD. The single-dose PK measures were Cmax (58.22±11.31), AUC0-18 (556.92±135.84), AUC0-36 (608.82±159.84), Tmax (6.48±3.78). In the multiple-dose study, PK findings were Cmax (73.20±17.71), AUC0-τ (714.36±303.21), Cτss (4.15±6.51), Tmaxss (5.60±3.12). Vildagliptin SR 50 mg achieved prolonged DPP-4 inhibition (≥80%) for18-20 hours after single and multiple-dose administration as compared to Galvus® (12-13 hours).Conclusions: Investigational vildagliptin SR tablet was found safe, well-tolerated after single and multiple-dose administration. Its extended DPP-4 inhibition profile compared to Galvus® may benefit the patient population on combination therapy with a sulphonylurea and renally impaired patients

Real world evidence of effectiveness and safety of an oral formulation containing un-denatured type-II collagen 40 mg and aflapin 100 mg (HAPID®) in the management of osteoarthritis of knee: findings of a prospective, multi-center, observational study

Background: Osteoarthritis (OA) of knee is a common progressive multifactorial joint disorder affecting the quality of life, and surgical repair is the final option which has substantial impact on healthcare costs. This real-world study evaluates the efficacy and safety of an oral formulation containing UC-II and aflapin (Boswellia serrata extract enriched in 3-O-acetyl-11-keto-beta-boswellic acid) for treatment of OA of knee.Methods: Data of 505 ambulatory adult patients (study duration-Jul-21 to Jul-22) of either gender (227 M, 278 F) having OA of knee, and who received study treatment (capsule HAPID®, Wockhardt, India) once daily for a period of up to 90 days were included for the study after obtaining informed written consent. Primary outcomes were mean change in Western Ontario and McMaster universities OA index (WOMAC) scores from baseline through day 90 (total and sub-scales for joint pain, joint stiffness, and physical function), and change in 0-10 visual analogue scale (VAS) score for pain.Results: About 285 (56.4%) patients were newly diagnosed, majority (63.4%) were having grade 2 severity of OA (Kellgren and Lawrence grade). The mean (SD) baseline total WOMAC scores improved from 60.94 (23.60) at baseline to 26.42 (22.19) on day 90. Significant improvements were seen starting from day 5 (p=0.023) and progressively up to day 90 (p<0.0001).Conclusions: The excellent safety and efficacy profile of combination therapy with aflapin and UC-II makes it a desirable pharmacological treatment modality for management of patients of knee OA

Modeling Changes in Hydrate Stability Associated with Arctic Warming and its Impact on Slope

If global warming continues at its current rate, widespread methane hydrate dissociation may occur leading to submarine slope instabilities. In this study, numerical models were developed to investigate the impact of different parameters, such as geothermal gradient, slope angle, rate of seafloor temperature rise, and hydrate saturation on the dissociated volume and potential for slope instabilities. It was found that the geothermal gradient impacts the shape of the hydrate stability zone and the pattern of hydrate dissociation. Slope stability analyses showed that steeper slopes fail earlier and produce lower dissociated hydrate volumes. Higher rate of seafloor temperature produces larger dissociated volume and leads to earlier slope failure. On the other hand, higher hydrate saturation leads to lower hydrate dissociated volume and causes to fail slope comparatively later than a slope with lower hydrate saturation