gemigliptin + metformin hydrochloride (ZemiMet / ZemiMet SR)

Spatial inequalities and contextual correlates of methylphenidate dispensing in Jiangsu Province, China.

Sun Yao Y, Lu Miao M, Zhang Yong Y, Xu Jin J et al.

Understanding geographic inequalities in psychotropic medication dispensing is important for improving health equity and informing place-based pharmaceutical management. This study characterized the spatiotemporal distribution of methylphenidate hydrochloride extended-release tablet dispensing in Jiangsu Province, China, from 2019 to 2023 and examined its socioeconomic and education-related correlates. Annual county-level dispensed tablet volumes were analyzed using Getis-Ord Gi* hot-spot analysis, standard deviational ellipses, and weighted-centroid analysis. Prefecture-level contextual correlates were examined using annual Lasso models interpreted with SHAP. The proportion of county-level units with zero recorded dispensing decreased from approximately 52%-36%, while the proportion with annual volumes exceeding 20,000 tablets increased from 7% to 20%. Southern Jiangsu consistently exhibited higher dispensing volumes than Northern Jiangsu, with Central Jiangsu generally occupying an intermediate position. Getis-Ord Gi* identified localized high-value concentrations mainly in Southern and parts of Central Jiangsu. The standard deviational ellipse area increased by 23.1%, while the weighted centroid remained in south-central Jiangsu. Within the annual Lasso models, predictive importance was allocated mainly to economic-demographic indicators in 2019-2020 and more strongly to education-related indicators in 2021-2023. The findings support geographically differentiated monitoring of medication access, dispensing patterns, and prescribing quality.

Correction to "Evidence of a Protective Effect of Metformin on Abdominal Aortic Aneurysm Risk: Insights from an Observational Study and Mendelian Randomisation Analysis Using Putative Metformin Targets".

Brixadi for Stimulant Use Disorder: Evolving Pharmacologic Considerations and Clinical Implications.

Sawaya M Farris MF, McNulty Molly E ME, Germain Collin J St CJS, Hachem Ibraheem A IA et al.

Substance use disorders are an increasing concern globally, causing a tremendous uptick in public health burden in recent years. Despite the growing attention these disorders receive, there remain no approved pharmacotherapies for stimulant use disorder, thereby contributing a major portion of this burden. This review examines the potential use of Brixadi, an extended-release injectable formulation of the widely used pharmacotherapy buprenorphine, indicated for opioid use disorder, in the treatment of stimulant use disorder. Psychostimulants, including cocaine, methamphetamine, and designer stimulants, all exert their effects by inhibiting or reversing the directionality of the monoamine transporters in the synaptic cleft. Inhibition or reversal of these transporters in the synaptic cleft allows dopamine, serotonin, and norepinephrine to remain in the synapse, which ultimately enhances their activity and contributes to the reinforcement of substance use. The reinforcement loop driven by excess neurotransmitters, particularly dopamine, provides a pharmacotherapeutic target via receptor interactions. Brixadi is an injectable extended-release buprenorphine primarily used to treat opioid use disorder. The extended-release mechanism enables sustained drug-receptor interaction, resulting in stable plasma drug concentrations. Buprenorphine is as a dual-acting agent, a partial μ-opioid receptor (MOR) agonist and a κ-opioid receptor (KOR) antagonist. KOR antagonism modulates symptoms of withdrawal in OUD, including dysphoria, stress, and drug cravings. Therefore, Brixadi's KOR antagonism may offer a promising pharmacologic target for stimulant use disorder recovery by mitigating these negative affective states. Additionally, the bimodal mechanism suggests that Brixadi may be a beneficial pharmacologic candidate for people who suffer from polysubstance use involving opioids and psychostimulants. While there is promise behind these developments, current studies are limited to preclinical trials and have not yet advanced toward clinical trials. However, Brixadi's extended-release profile and potential capability to minimize withdrawal-related dysphoria and stress-induced drug seeking present promise for further clinical investigation.

Ethosomal Gel-Based Topical Delivery of Albendazole Hydrochloride for Psoriasis: In Vitro and In Vivo Evaluation.

Rençber Seda S, Karpuz Merve M, Ünlü Çakıcı Büşra B, Karayıldırım Çinel Köksal ÇK et al.

This study aimed to develop an albendazole hydrochloride (ALB)-loaded ethosomal gel for topical psoriasis treatment. ALB-loaded ethosomes were prepared and characterized to select the optimal formulation, which was subsequently incorporated into an HPMC-based hydrogel. The ethosomal gel was evaluated through physicochemical, in vitro and in vivo studies. The optimized ethosomal formulation prepared by the film hydration method exhibited a mean vesicle size of 490.00 ± 0.14 nm, polydispersity index of 0.31 ± 0.14, zeta potential of -22.85 ± 2.28 mV and encapsulation efficiency of 23.90 ± 1.43%. After incorporation into the hydrogel matrix, the Gel4-E3/ALB formulation demonstrated appropriate mechanical properties (hardness 8.42 ± 0.70 mN, adhesiveness - 16.85 ± 1.50 mN·s, elasticity 0.89 ± 0.07, cohesiveness 1.14 ± 0.09) and shear-thinning behavior, ensuring ease of application and skin retention. A controlled release pattern was observed, consistent with the controlled-release behavior expected from ethosomal hydrogel systems. Radiolabeling studies demonstrated high labeling efficiency (> 95%). In vitro cytotoxicity evaluation indicated that the optimized ethosomal gel formulation was non-toxic. In vivo studies performed in an imiquimod (IMQ)-induced psoriatic mouse model revealed significant therapeutic improvement in the Gel4-E3/ALB-treated group compared with the IMQ control, with visible reduction in erythema, scaling, and skin thickening after the fifth day of treatment. Hematological analysis showed no adverse effects associated with the formulation. Histopathological evaluation confirmed the reduction in epidermal hyperplasia and inflammatory cell infiltration in the treated group. The developed ALB-loaded ethosomal gel represents a safe and promising topical therapeutic system for psoriasis management.