Pharmacokinetic comparison between tablet of varenicline tartrate and orally disintegrating film of varenicline salicylate in healthy subjects.

OBJECTIVE: Varenicline is an efficacious aid for smoking cessation. In this study, the pharmacokinetics and safety were compared between film-coated tablets of varenicline tartrate (reference drug) and the newly developed orally disintegrating films of varenicline salicylate (test drug), both of them contained 1 mg of varenicline. MATERIALS AND METHODS: A randomized, open-label, single-dose, two-sequence, two-period crossover study was conducted in healthy male subjects. Serial blood samples were obtained for up to 72 hours in each period, with a washout period of 7 days or more. The pharmacokinetic parameters were calculated using the noncompartmental method. Safety profiles were assessed throughout the study. RESULTS: A total of 28 subjects completed the study. The plasma varenicline concentration-time profiles were similar for the two study drugs. The maximum plasma varenicline concentration (Cmax) was 5,768.95 ng/L (mean) and 5,780.55 ng/L for the test drug and reference drug, respectively. The areas under the concentration-time curve from time 0 to the last measurable time point (AUC0-t) were 94,086.30 h×ng/L and 89,958.55 h×ng/L for the test drug and reference drug, respectively. The geometric mean ratios (90% confidence intervals) of the test drug to the reference drug for Cmax and AUC0-t were 0.9955 (0.9488 - 1.0444) and 1.0449 (0.9848 - 1.1088), respectively, which fell within the bioequivalence range of 0.8 - 1.25. There was no difference in safety between the study drugs. CONCLUSION: The pharmacokinetics and safety profiles were similar between the two study drugs. The orally disintegrating film of varenicline salicylate can be an alternative to varenicline tartrate tablets.

Comparison of the pharmacokinetic characteristics and bioequivalence between two nanosuspension formulations of megestrol acetate in healthy Korean male subjects.

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence. Trial Registration: ClinicalTrials.gov Identifier: NCT06147908.

Evaluating the Relationships between Riparian Land Cover Characteristics and Biological Integrity of Streams Using Random Forest Algorithms.

The relationships between land cover characteristics in riparian areas and the biological integrity of rivers and streams are critical in riparian area management decision-making. This study aims to evaluate such relationships using the Trophic Diatom Index (TDI), Benthic Macroinvertebrate Index (BMI), Fish Assessment Index (FAI), and random forest regression, which can capture nonlinear and complex relationships with limited training datasets. Our results indicate that the proportions of land cover types in riparian areas, including urban, agricultural, and forested areas, have greater impacts on the biological communities in streams than those offered by land cover spatial patterns. The proportion of forests in riparian areas has the greatest influence on the biological integrity of streams. Partial dependence plots indicate that the biological integrity of streams gradually improves until the proportion of riparian forest areas reach about 60%; it rapidly decreases until riparian urban areas reach 25%, and declines significantly when the riparian agricultural area ranges from 20% to 40%. Overall, this study highlights the importance of riparian forests in the planning, restoration, and management of streams, and suggests that partial dependence plots may serve to provide insightful quantitative criteria for defining specific objectives that managers and decision-makers can use to improve stream conditions.

Spatially Varying and Scale-Dependent Relationships of Land Use Types with Stream Water Quality.

Understanding the complex relationships between land use and stream water quality is critical for water pollution control and watershed management. This study aimed to investigate the relationship between land use types and water quality indicators at multiple spatial scales, namely, the watershed and riparian scales, using the ordinary least squares (OLS) and geographically weighted regression (GWR) models. GWR extended traditional regression models, such as OLS to address the spatial variations among variables. Our results indicated that the water quality indicators were significantly affected by agricultural and forested areas at both scales. We found that extensive agricultural land use had negative effects on water quality indicators, whereas, forested areas had positive effects on these indicators. The results also indicated that the watershed scale is effective for management and regulation of watershed land use, as the predictive power of the models is much greater at the watershed scale. The maps of estimated local parameters and local R2 in GWR models showcased the spatially varying relationships and indicated that the effects of land use on water quality varied over space. The results of this study reinforced the importance of watershed management in the planning, restoration, and management of stream water quality. It is also suggested that planners and managers may need to adopt different strategies, considering watershed characteristics-such as topographic features and meteorological conditions-and the source of pollutants, in managing stream water quality.

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen.

OBJECTIVE: Prostaglandin E2 (PGE2) synthesis is modulated by COX2. Changes in PGE2 could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects. MATERIALS AND METHODS: A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2 inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2 was applied to the pharmacodynamic evaluation. RESULTS: After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration-time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2 WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%. CONCLUSION: Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.