Class Of Drugs Research Articles

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.

The multifaceted effects of flavonoids on neuroplasticity.

There has been a significant increase in the incidence of multiple neurodegenerative and terminal diseases in the human population with life expectancy increasing in the current times. This highlights the urgent need for a more comprehensive understanding of how different aspects of lifestyle, in particular diet, may affect neural functioning and consequently cognitive performance as well as in enhancing overall health. Flavonoids, found in a variety of fruits, vegetables, and derived beverages, provide a new avenue of research that shows a promising influence on different aspects of brain function. However, despite the promising evidence, most bioactive compounds lack strong clinical research efficacy. In the current scoping review, we highlight the effects of Flavonoids on cognition and neural plasticity across vertebrates and invertebrates with special emphasis on the studies conducted in the pond snail, Lymnaea stagnalis, which has emerged to be a functionally dynamic model for studies on learning and memory. In conclusion, we suggest future research directions and discuss the social, cultural, and ethnic dependencies of bioactive compounds that influence how these compounds are used and accepted globally. Bridging the gap between preclinical and clinical studies about the effects of bioactive natural compounds on brain health will surely lead to lifestyle choices such as dietary Flavonoids being used complementarily rather than as replacements to classical drugs bringing about a healthier future.

First, a seat; then, an upgrade.

The Sir Stanley Peart Essay Competition is an annual event run by the British and Irish Hypertension Society to encourage Early Career Researchers to continue the ethos of Sir Stanley Peart. Sir Stanley Peart was a clinician and clinical researcher who made a major contribution to our understanding of blood pressure regulation. He was the first to demonstrate the release of noradrenaline in response to sympathetic nerve stimulation. He was also the first to purify, and determine the structure of, angiotensin and he later isolated the enzyme, renin, and carried out many important investigations of the factors controlling its release in the body. This year, the essay topic was "Do we need new classes of antihypertensive drugs?". In his prize-winning essay, "First, a seat; then, an upgrade", Dr Sathyanarayanan argues that we do not need new classes of antihypertensive drugs, instead we should focus our attention on addressing the factors that lead to high blood pressure in the first place and use our existing drug classes more effectively.

Central nervous system active medication use in Medicare enrollees receiving home health care: association with chronic pain and anxiety level.

No comparative effectiveness data exist on nonopioid analgesics and nonbenzodiazepine anxiolytics to treat pain with anxiety. We examined the relationship between drug class and central nervous system (CNS) active drug polypharmacy on pain and anxiety levels in Medicare enrollees receiving home health (HH) care. This retrospective cohort study included enrollees with diagnoses and 2+ assessments of pain and anxiety between HH admission and discharge. Three sets of linear regression difference-in-reduction analyses assessed the association of pain or anxiety reduction with number of drugs; drug type; and drug combinations in those with daily pain and daily anxiety. Logistic regression analysis assessed the effect of medication number and class on less-than-daily pain or anxiety at HH discharge. A sensitivity analysis using multinomial regression was conducted with a three-level improvement to further determine clinical significance. Of 85,403 HH patients, 43% received opioids, 27% benzodiazepines, 26% gabapentinoids, 32% selective serotonin reuptake inhibitors, and 8% serotonin and norepinephrine reuptake inhibitors (SNRI). Furthermore, 75% had depression, 40% had substance use disorder diagnoses, and 6.9% had PTSD diagnoses. At HH admission, 83%, 35%, and 30% of patients reported daily pain, daily anxiety, and both, respectively. Central nervous system polypharmacy was associated with worse pain control and had no significant effect on anxiety. For patients with daily pain plus anxiety, pain was best reduced with one medication or any drug combination without opioid/benzodiazepine; anxiety was best reduced with combinations other than opiate/benzodiazepine. Gabapentinoids or SNRI achieved clinically meaningful pain control. Selective serotonin reuptake inhibitors provided clinically meaningful anxiety relief.

Central nervous system active medication use in Medicare enrollees receiving home health care: association with chronic pain and anxiety level.

No comparative effectiveness data exist on nonopioid analgesics and nonbenzodiazepine anxiolytics to treat pain with anxiety. We examined the relationship between drug class and central nervous system (CNS) active drug polypharmacy on pain and anxiety levels in Medicare enrollees receiving home health (HH) care. This retrospective cohort study included enrollees with diagnoses and 2+ assessments of pain and anxiety between HH admission and discharge. Three sets of linear regression difference-in-reduction analyses assessed the association of pain or anxiety reduction with number of drugs; drug type; and drug combinations in those with daily pain and daily anxiety. Logistic regression analysis assessed the effect of medication number and class on less-than-daily pain or anxiety at HH discharge. A sensitivity analysis using multinomial regression was conducted with a three-level improvement to further determine clinical significance. Of 85,403 HH patients, 43% received opioids, 27% benzodiazepines, 26% gabapentinoids, 32% selective serotonin reuptake inhibitors, and 8% serotonin and norepinephrine reuptake inhibitors (SNRI). Furthermore, 75% had depression, 40% had substance use disorder diagnoses, and 6.9% had PTSD diagnoses. At HH admission, 83%, 35%, and 30% of patients reported daily pain, daily anxiety, and both, respectively. Central nervous system polypharmacy was associated with worse pain control and had no significant effect on anxiety. For patients with daily pain plus anxiety, pain was best reduced with one medication or any drug combination without opioid/benzodiazepine; anxiety was best reduced with combinations other than opiate/benzodiazepine. Gabapentinoids or SNRI achieved clinically meaningful pain control. Selective serotonin reuptake inhibitors provided clinically meaningful anxiety relief.

Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway.

People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs). From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB). From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0-1.52) vs. 0‰ (IQR 0-0.46) (p<0.001). GHB was not detected. Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.

Black phosphorus quantum dots prevent atherosclerosis in high-fat diet-fed apolipoprotein E knockout mice.

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases such as coronary heart disease. Black phosphorus quantum dots (BPQDs) are a novel nanomaterial with good optical properties and biocompatibility, which was applied in the treatment of AS in mice, with good results shown in our previous study. In this study, BPQDs were injected into high-fat diet-fed apolipoprotein E knockout mice as a preventive drug for 12 weeks. Simvastatin, a classic preventive drug for AS, was used as a control to verify the preventive effect of BPQDs. The results showed that after preventive treatment with BPQDs, the plaque area in mice was significantly reduced, the vascular elasticity was increased, and serum lipid levels were significantly lower than those in the model group. To explore the mechanism, macrophages were induced to become foam cells using oxidized low-density lipoprotein. We found that BPQDs treatment could increase cell autophagy, thereby regulating intracellular lipid metabolism. Taken together, these data revealed that BPQDs may serve as a functional drug in preventing the development of AS.

Impact of the COVID-19 Pandemic on Pharmacist Interventions: A Retrospective Study with Inpatients in a University Hospital.

Despite growing interest in understanding the challenges faced by multidisciplinary health teams during the COVID-19 pandemic, there is a lack of studies specifically focusing on changes in pharmacist interventions and drug-related problems. To analyze and compare the interventions performed by pharmacists during comprehensive medication management in the adult intensive care unit and general internal medicine ward of the University Hospital of the University of São Paulo, Brazil, for defined periods before the onset of the COVID-19 pandemic and during the pandemic itself. All pharmacist interventions performed in relation to inpatient prescriptions from March to December 2019 (before the pandemic) and from March to December 2021 (during the pandemic) were collected and tabulated. These interventions were then classified according to the Pharmaceutical Care Network Europe (PCNE) system, version 9.1, and categorized based on first-level codes of the Anatomical Therapeutic Chemical classification system. The analysis revealed substantial changes in the patterns of pharmacist interventions and the therapeutic classes of drugs for COVID-19-positive and COVID-19-negative patients during the pandemic relative to patients in the pre-pandemic period. Among COVID-19-positive patients, interventions were predominantly related to enhancing patient safety (PCNE code P2), drug selection (C1), dose selection (C3), prescribing and dispensing processes (C5), the drug-use process (C6), and patient transfers between different levels of care (C8). The drug-related problems addressed by pharmacist interventions primarily involved COVID-19-positive patients in the pandemic period and were related to systemic hormonal preparations (excluding sex hormones and insulins), anti-infective agents for systemic use, nervous system and drugs for the blood and blood-forming organs. The results of this study highlight the adaptability and competence of pharmacists in responding to critical scenarios such as the COVID-19 pandemic. These scenarios are characterized by new work dynamics, the hiring of additional professionals, an increase in the number of beds, the rapid evolution of evidence-based information, and drug shortages that necessitate the use of alternative medications. Pharmacists play a crucial role in ensuring patient safety during these difficult times.

Nirmatrelvir-Ritonavir (Paxlovid)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses nirmatrelvir-ritonavir (Paxlovid), 150 mg nirmatrelvir; 100 mg ritonavir, tablets, co-packaged for oral use. Indication: For the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Immunity in digestive diseases: new drugs for inflammatory bowel disease treatment-insights from Phase II and III trials.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), continues to challenge treatment paradigms. Advancements in therapeutic options have been have been driven by Phase 2 and 3 clinical trials of new drug classes, particularly sphingosine-1-phosphate (S1P) modulators and interleukin-23 (IL-23) inhibitors. This review synthesizes findings from Phase 2 and 3 clinical trials conducted up to early 2024, focusing on the impact of S1P modulators and IL-23 inhibitors on IBD management. Drugs such as ozanimod, etrasimod, risankizumab, mirikizumab, guselkumab, and brasikumab were evaluated for their efficacy and safety profiles. S1P modulators, such as ozanimod and etrasimod, effectively regulate immune cell trafficking to reduce inflammation and several trials highlight their clinical effectiveness in both inducing and maintaining remission in IBD, highlighting its long-term safety and sustained therapeutic effects. Additionally, IL-23 inhibitors including risankizumab, mirikizumab, and guselkumab, which disrupt key inflammatory cytokine pathways, have already shown significant effectiveness in inducing and maintaining remission in both CD and UC, with favorable safety profiles across multiple studies, suggesting their potential as critical components in managing IBD. The clinical trials indicate that both S1P modulators and IL-23 inhibitors offer promising therapeutic benefits and maintain strong safety profiles, positioning them as potential cornerstone treatments for IBD. Despite these advancements, further exploration into long-term safety and the development of personalized treatment strategies is essential for maximizing clinical outcomes.

Krüppel-like Factor 2 is an endo-protective transcription factor in diabetic kidney disease.

Diabetic kidney disease (DKD) is a microvascular complication of diabetes, and glomerular endothelial cell (GEC) injury is a key driver of DKD pathogenesis. Krüppel-like factor 2 (KLF2), a shear stress-induced transcription factor, was identified among the genes that are highly upregulated in early DKD. In the kidney, KLF2 expression is mostly restricted to endothelial cells, but its expression is also found in immune cell subsets. KLF2 expression is upregulated in response to increased shear stress by the activation of mechanosensory receptors, but suppressed by inflammatory cytokines, both of which characterize the early diabetic kidney milieu. KLF2 expression is reduced in progressive DKD and hypertensive nephropathy in humans and mice, likely due to high glucose and inflammatory cytokines such as TNF-α. However, KLF2 expression is increased in settings of glomerular hyperfiltration-induced shear stress without metabolic dysregulation, such as in settings of unilateral nephrectomy. Lower KLF2 expression is associated with CKD progression in patients with unilateral nephrectomy, consistent with its endoprotective role. KLF2 confers endoprotection by inhibition of inflammation, thrombotic activation, and angiogenesis, and thus KLF2 is considered a protective factor for cardiovascular disease (CVD). Based on similar mechanisms, KLF2 also exhibits renoprotection, and its reduced expression in endothelial cells worsens glomerular injury and albuminuria in settings of diabetes or unilateral nephrectomy. Thus, KLF2 confers endo-protective effects in both CVD and DKD, and its agonists could be potentially developed as a novel class of drugs for cardio-renal protection in diabetic patients.

Antidepressant and antipsychotic prescribing in patients with type 2 diabetes in Scotland: A time-trend analysis from 2004 to 2021.

Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D. We conducted repeated annual cross-sectional analysesof a population-based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross-sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype. The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person-years to 33.3 per 100 person-years and from 2.8 per 100 person-years to 4.7 per 100 person-years, respectively). We observed this pattern for all drug subtypes except for first-generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class. There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration.

Antidepressant and antipsychotic prescribing in patients with type 2 diabetes in Scotland: A time-trend analysis from 2004 to 2021.

Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D. We conducted repeated annual cross-sectional analysesof a population-based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross-sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype. The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person-years to 33.3 per 100 person-years and from 2.8 per 100 person-years to 4.7 per 100 person-years, respectively). We observed this pattern for all drug subtypes except for first-generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class. There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration.

Salbutamol, a Short Acting Beta-2 Agonist, Reduces Risk and Improves Prognosis of Prostate Cancer.

Beta-blockers, a class of drugs commonly used to manage blood pressure, have been the subject of research regarding their relationship to prostate cancer (PC) risk, prognosis, and treatment. Beta-blockers reduce risk and improve the prognosis of PC. Perioperative use of a nonselective beta-blocker improves outcomes after radical prostatectomy. However, a related class of drugs, beta-2 adrenergic agonists, has received little attention in PC. We studied the relationship of the beta-2 adrenergic agonist salbutamol to PC risk and survival. We analyzed Food and Drug Administration MedWatch data to determine whether salbutamol could influence the risk of PC. We used UK Biobank data to assess the effect of salbutamol on PC survival. Salbutamol significantly reduces PC risk, proportional reporting ratio, and 95% CI (lower bound; upper bound): 0.131 (0.11; 0.155) and improves prognosis. Mean survival was 7.35 years for subjects not taking salbutamol, and 10.5 years for subjects taking salbutamol (P = 0.041, log-rank test. To adjust for the effect of age, we performed proportional hazards regression, survival time-dependent variable, age, and salbutamol use independent variables. Salbutamol use was significantly related to survival time (P = 0.016) and independent of the significant effect of age (P < 0.001). We found a lower proportion of PCs in salbutamol-treated people, but we have not demonstrated that PC risk is reduced (there is no proof of causality). There is no causality relationship between salbutamol and the survival of patients with PC treated with salbutamol versus those not treated with the drug. Yet, there is a trend in favor of salbutamol-treated patient survival. Therefore, salbutamol and other beta-adrenergic agonists might represent a new class of drugs for the treatment of PC.

Prescription Patterns in Jails Before and Since the COVID-19 Pandemic: A Multisite Serial Cross-Sectional Investigation.

In response to the COVID-19 pandemic, jails were advised to reduce facility census, particularly the growing population of those with medical/behavioral health vulnerabilities that increased susceptibility to adverse outcomes. Although jail census decreased across the nation in the initial days to months following pandemic declaration, there are minimal data regarding the health status of those who remained in jail. The current investigation aspired to describe jail census trends before/since the onset of COVID-19 and offer snapshots of temporal changes and context for prevalence estimates of medical/behavioral health conditions in jail detainees from 2019 to 2023. Using a serial cross-sectional design, prescription information for individuals residing in 18 jails across the United States on June 30 of each respective year was extracted and categorized using MediSpan's ontological system to determine prevalence estimates of prescribed agents/products. Although data evidenced an initial 31% census reduction (followed by gradual return to prepandemic rates), prescribing patterns for all major therapeutic drug classes steadily increased, with 10% more individuals prescribed at least one agent in 2023 than 2019. The largest increases were observed for behavioral health agents (e.g., 32.4% of the sample was prescribed psychotropic agents in 2023 compared with 25.7% in 2019). We provide considerations for future investigations.

Biologics in Focus: A Comprehensive Review of Current Biological and Small Molecules Therapies for Crohn’s Disease in the United Arab Emirates (UAE)

Introduction: The management of Crohn’s disease (CD) in the Middle East, like in other parts of the world, is rapidly evolving with the introduction of novel advanced medical and biological therapies. In the United Arab Emirates (UAE), several biological therapies are used to achieve remission in severe and resistant cases of CD. We carried out a literature search to analyze the effectiveness and safety of biologic treatments currently licensed in the UAE. Methods: We searched the PubMed, Embase and Cochrane library databases from inception to January 2020 to identify relevant studies. Search terms were generated using established treatment guidelines for CD. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: Biologic and small molecule agents for CD include four core drug classes: anti-tumor necrosis factor-α agents (TNF-α), integrin receptor antagonists, Janus kinase (JAK) inhibitors and IL-12/IL-23 antagonists. All drug classes showed good efficacy and safety in managing patients with CD. Some drug classes had distinguishable side effect profiles. This included an increased lymphoma and tuberculous risk for TNF-α and integrin receptor antagonists. Many trials supported the effectiveness of these licensed drugs. Biologic agent intolerance was common; one-third of patients receiving TNF-α treatment will develop intolerance to that specific drug. Conclusions: Advanced medical therapies licensed in the UAE have proven to be safe and efficacious. Additional research is required to evaluate the safety and efficacy of newer biologics and biosimilars.

Biologics in Focus: A Comprehensive Review of Current Biological and Small Molecules Therapies for Crohn’s Disease in the United Arab Emirates (UAE)

Introduction: The management of Crohn’s disease (CD) in the Middle East, like in other parts of the world, is rapidly evolving with the introduction of novel advanced medical and biological therapies. In the United Arab Emirates (UAE), several biological therapies are used to achieve remission in severe and resistant cases of CD. We carried out a literature search to analyze the effectiveness and safety of biologic treatments currently licensed in the UAE. Methods: We searched the PubMed, Embase and Cochrane library databases from inception to January 2020 to identify relevant studies. Search terms were generated using established treatment guidelines for CD. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: Biologic and small molecule agents for CD include four core drug classes: anti-tumor necrosis factor-α agents (TNF-α), integrin receptor antagonists, Janus kinase (JAK) inhibitors and IL-12/IL-23 antagonists. All drug classes showed good efficacy and safety in managing patients with CD. Some drug classes had distinguishable side effect profiles. This included an increased lymphoma and tuberculous risk for TNF-α and integrin receptor antagonists. Many trials supported the effectiveness of these licensed drugs. Biologic agent intolerance was common; one-third of patients receiving TNF-α treatment will develop intolerance to that specific drug. Conclusions: Advanced medical therapies licensed in the UAE have proven to be safe and efficacious. Additional research is required to evaluate the safety and efficacy of newer biologics and biosimilars.

Assessment of subcutaneously administered insulins using in vitro release cartridge: Medium composition and albumin binding

Biotherapeutics is the fastest growing class of drugs administered by subcutaneous injection. In vitro release testing mimicking physiological conditions at the injection site may guide formulation development and improve biopredictive capabilities. Here, anin vitrorelease cartridge (IVR cartridge) comprising a porous agarose matrix emulating subcutaneous tissue was explored. The objective was to assess effects of medium composition and incorporation of human serum albumin into the matrix. Drug disappearance was assessed for solution, suspension and in situ precipitating insulin products (Actrapid, Levemir, Tresiba, Mixtard 30, Insulatard, Lantus) using the flow-based cartridge. UV–Vis imaging and light microscopy visualized dissolution, precipitation and albumin binding phenomena at the injection site. Divalent cations present in the release medium resulted in slower insulin disappearance for suspension-based and in situ precipitating insulins. Albumin-binding acylated insulin analogs exhibited rapid disappearance from the cartridge; however, sustained retention was achieved by coupling albumin to the matrix. An in vitro-in vivorelation was established for the non-albumin-binding insulins.The IVR cartridge is flexible with potential in formulation development as shown by the ability to accommodate solutions, suspensions, and in situ forming formulations while tailoring of the system to probe in vivo relevant medium effects and tissue constituent interactions.

Preparation of nanoparticle and nanoemulsion formulations containing repaglinide and determination of pharmacokinetic parameters in rats

Repaglinide (RPG) belongs to the class of drugs known as meglitinides and is used for improving and maintaining glycemic control in the treatment of patients with Type 2 diabetes. RPG is a Class II drug (BCS) because of its high permeability and low water solubility. It also undergoes hepatic first-pass metabolism. The oral bioavailability of RPG is low (about 56 %) due to these drawbacks. Our aim in this study is to prepare two different nano-sized drug carrier systems containing RPG (nanoparticle: RPG-PLGA-Zein-NPs or nanoemulsion: RPG-NE) and to carry out a pharmacokinetic study for these formulations. We prepared NPs using PLGA and Zein. In addition, a single NE formulation was developed using Tween 80 and Pluronic F68 as surfactants and Labrasol as co-surfactant. The droplet size values of the blank-NE and RPG-NE formulations were found to be less than 120 nm. The mean particle sizes of blank-Zein-PLGA-NPs and RPG-Zein-PLGA-NPs were less than 260 nm. The Cmax and tmax values of RPG-Zein-PLGA-NPs and RPG-NE (523 ± 65 ng/mL and 770 ± 91 ng/mL; 1.41 ± 0.46 h and 1.61 ± 0.37 h, respectively) were meaningfully higher than those of free RPG (280 ± 33 ng/mL; 0.72 ± 0.28 h) (p < 0.05). The AUC0-∞ values calculated for RPG-Zein-PLGA-NPs and RPG-NE were approximately 4.04 and 5.05 times higher than that calculated for free RPG. These nanosized drug delivery systems were useful in increasing the oral bioavailability of RPG. Moreover, the NE formulation was more effective than the NP formulation in improving the oral bioavailability of RPG (p < 0.05).

Fentanyl-Related Deaths in Ontario, Canada: Toxicological Findings and Circumstances of Death in 4395 Cases (2020-2022).

Over the last 20 years there has been a significant increase in fentanyl related deaths in Ontario, Canada. This report examines toxicological findings in a series of death investigations in which fentanyl was quantitated to identify the prevalence, trends and demographic data associated with fentanyl in Ontario, Canada, and to highlight the changes in these trends since fentanyl began appearing in casework in Ontario in the early 2000s. A retrospective study of all cases in which fentanyl was quantitated in blood, using liquid chromatography-tandem mass spectrometry, was conducted for the time period between January 1, 2020, and December 31, 2022. A total of 4395 cases were included, 77% of the decedents were male and 23% were female with ages ranging from 0 to 95. The most frequently classified cause of death was mixed drug toxicity (69%) followed by fentanyl intoxication at 19%. Less than 10% of cases where fentanyl was quantitated were classified as non-drug related deaths. Fentanyl concentrations in all cases ranged from 1.3 to > 2000 ng/mL. Other drugs were frequently detected with fentanyl. In mixed drug toxicity cases, stimulants were the most frequently encountered class of drugs: cocaine was identified in 51.8% and methamphetamine was observed in 43.0% of cases, respectively. Detailed reports for select cases were included to provide additional insight into the different case types and to show the difficulty in interpreting blood concentrations without additional detailed case histories. This study provides valuable information for the scientific and medical community regarding the continued use of fentanyl and how patterns of fentanyl use have evolved since it began to appear in forensic casework.