Dose-Response Evaluation of Scopoletin, a Phytochemical, in a High-Fructose High-Fat Diet-Induced Dyslipidemia Model in Wistar Rats.

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II-VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III-VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial.

A study to explore the appropriateness of dosing regimen of vancomycin in critically ill patients in a tertiary care unit of India.

Introduction: Vancomycin is used in proven or suspected MRSA and MRE infections. An AUC/MIC ratio of ≥400 is the current accepted critical PK/PD"efficacy" target of vancomycin activity. The present study was conducted to ascertain the appropriateness of practice of current dosage regimen of vancomycin (1 g BD) based on population pharmacokinetic approach. Methods: A single-center prospective study with the ICU setting of a tertiary care center was conducted. A total of 15 adult patients with sepsis treated with vancomycin were included over 15 months from May 2019 to July 2020. Blood samples were obtained at 5, 10, and 30 minutes and thereafter at 2 and 6 hours following the completion of the vancomycin infusion. The data obtained from HPLC estimation was analyzed using a population pharmacokinetic approach with NLME, Phoenix 8.3.2.166. The pharmacokinetic model was based on covariates such as bodyweight and urinary creatinine clearance to predict drug concentrations. Results: A total of 83 vancomycin blood samples were analyzed. The mean AUC0-last and AUC0-∞ in patients who improved and died were (AUC(0-last)=293 (152.97); AUC(0-∞)=535.14 (353.67) and (AUC(0-last)=137.19 (51.37); AUC(0-∞)=582.12 (1036.09) respectively, the difference between the two outcome groups was not statistically significant (p=0.104). The pharmacokinetic model was best described by a two-compartment linear model. The goodness-of-fit plots showed that the final covariate pharmacokinetic model (having bodyweight and urinary creatinine clearance) adequately described the observed vancomycin concentrations. Conclusions: Based on the finding of the study it was concluded that 1 g BD dosing of vancomycin is inappropriate. Including covariates such as urinary creatinine clearance and weight in the pharmacokinetic model helped predict drug concentrations more accurately. However, further studies are required to demonstrate efficacy regarding applying this strategy.

Single ascending dose safety, tolerability, and pharmacokinetic study of econazole in healthy volunteers.

INTRODUCTION: Econazole has been found efficacious as antitubercular in in vitro and in vivo animal studies. However, limited information is available for its safety and pharmacokinetics in humans. In our present study we have conducted single ascending dose, safety, and pharmacokinetic evaluation in healthy human volunteers with the purpose of enabling translation for tuberculosis. METHODS: This study was conducted as a single-center, ascending-dose, placebo-controlled, double blind design. Three ascending dose were chosen (250 , 500 , and 1000 mg) to be administered as a single oral dose. The volunteers were screened for potential eligibility. Participants were randomized to receive either Econazole or Placebo in a 6:2 design. Safety assessments and pharmacokinetic evaluations were carried out for each cohort. RESULTS: Econazole was found to be safe at all dose levels. No serious or severe adverse events occurred during the study. The AUC (0-∞) showed a response relationship with a value of 49 ± 3.47 h* µg/ml, 17. 86 ± 8.40 hr* µg/ml, 35.54 ± 13.94 hr* µg/ml for 250 mg, 500 mg, and 1000 mg, respectively. CONCLUSION: Based on the findings of our study, a dose of 500 mg Econazole, once a day orally was considered as appropriate for further evaluation.

Naturalistic Evaluation of Prescription Pattern in Glaucoma Clinic of a Tertiary Care Hospital: A Developing Country's Perspective.

BACKGROUND: Glaucoma is a chronic, gradual and progressive eye disorder characterized by visual loss and involving the typical changes in optic nerves and associated structures. Currently, the mainstay treatment lies in the reduction of intraocular pressure (IOP) involving the usage of two or three medications concurrently. However, prescription pattern of antiglaucoma drugs remains largely unstudied so far. Therefore, there is a dire need of drug utilization studies to ensure rational prescribing for better treatment outcomes. AIM: This study was conducted to assess the prescription pattern in glaucoma patients to encourage rational use of drugs. MATERIALS AND METHODS: The pertinent data of confirmed glaucoma patients were entered in a predesigned case record form (CRF) including patient demographic details, type of glaucoma, number of drug prescribed, drug dosage and dosage formulation with prior patient consent, and finally, the data were analyzed using Microsoft Excel. RESULTS: A total of 247 glaucoma patients were recorded in the study. The mean SD number of drugs per prescription was 2.18 (1.68). Monotherapy was prescribed to 72 (29.15%) patients, and the most common monotherapy prescribed was timolol, whereas in fixed-dose combinations (FDCs), brimonidine and timolol FDCs were most commonly encountered. Furthermore, prescriptions consisting of generic drugs only and prescribed as per the National List of Essential Medicines (NLEM) were 48 (19.43%) and 41 (16.59%), respectively. CONCLUSION: This study showed the judicious use of medications in tune with principles of rational drug use in our center, and the rationale practices can be extended to the peripheral centers of the country for better drug utilization.

Assessment of Appropriateness of Antimicrobial Therapy in Resource-Constrained Settings: Development and Piloting of a Novel Tool-AmRAT.

Inappropriate antimicrobial prescribing is considered to be the leading cause of high burden of antimicrobial resistance (AMR) in resource-constrained lower- and middle-income countries. Under its global action plan, the World Health Organization has envisaged tackling the AMR threat through promotion of rational antibiotic use among prescribers. Given the lack of consensus definitions and other associated challenges, we sought to devise and validate an Antimicrobial Rationality Assessment Tool-AmRAT-for standardizing the assessment of appropriateness of antimicrobial prescribing. A consensus algorithm was developed by a multidisciplinary team consisting of intensivists, internal medicine practitioners, clinical pharmacologists, and infectious disease experts. The tool was piloted by 10 raters belonging to three groups of antimicrobial stewardship (AMS) personnel: Master of Pharmacology (M.Sc.) (n = 3, group A), Doctor of Medicine (MD) residents (n = 3, group B), and DM residents in clinical pharmacology (n = 4, group C) using retrospective patient data from 30 audit and feedback forms collected as part of an existing AMS program. Percentage agreement and the kappa (κ) coefficients were used to measure inter-rater agreements amongst themselves and with expert opinion. Sensitivity and specificity estimates were analyzed comparing their assessments against the gold standard. For the overall assessment of rationality, the mean percent agreement with experts was 76.7% for group A, 68.9% for group B, and 77.5% for group C. The kappa values indicated moderate agreement for all raters in group A (κ 0.47-0.57), and fair to moderate in group B (κ 0.22-0.46) as well as group C (κ 0.37-0.60). Sensitivity and specificity for the same were 80% and 68.6%, respectively. Though evaluated by raters with diverse educational background and variable AMS experience in this pilot study, our tool demonstrated high percent agreement and good sensitivity and specificity, assuring confidence in its utility for assessing appropriateness of antimicrobial prescriptions in resource-constrained healthcare environments.