Vedolizumab Clearance as a Surrogate Marker for Remission in Inflammatory Bowel Disease Patients: Insights from Real-World Pharmacokinetics.

Vedolizumab (VDZ) is approved in the treatment of patients with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). VDZ exhibits considerable variability in its pharmacokinetic (PK) profile, and its exposure-response relationship is not yet fully understood. The aim was to investigate the variability in VDZ trough levels and PK parameters, to assess the relationship between VDZ PK and biochemical response, as well as clinical and endoscopic outcomes.

Antiplatelet Drugs Use in Pregnancy-Review of the Current Practice and Future Implications.

When clinicians opt for antithrombotic therapy to manage or prevent thrombotic complications during pregnancy, it is imperative to consider the unique physiological state of the pregnant woman's body, which can influence the pharmacokinetics of the drug, its ability to traverse the placental barrier, and its potential teratogenic effects on the fetus. While the efficacy and safety of aspirin during pregnancy have been relatively well-established through numerous clinical studies, understanding the effects of newer, more potent antiplatelet agents has primarily stemmed from individual clinical case reports necessitating immediate administration of potent antiplatelet therapy during pregnancy. This review consolidates the collective experiences of clinicians confronting novel thrombotic complications during pregnancy, often requiring the use of dual antiplatelet therapy.

Integrating Clopidogrel's First-Pass Effect in a Joint Semi-Physiological Population Pharmacokinetic Model of the Drug and Its Inactive Carboxylic Acid Metabolite.

Clopidogrel (CLO), a pro-drug for preventing thrombotic events, undergoes rapid absorption and extensive metabolism, with approximately 85-90% converted to an inactive carboxylic acid metabolite (CLO-CA) and the remaining to an active thiol (CLO-TH). Few pharmacokinetic models for the drug and its metabolites exist, with most focusing on CLO-TH. Although CLO-CA is inactive, its predominant (compared to its parent drug and metabolites) presence in plasma underscores the importance of characterizing its formation and pharmacokinetic profile.

Thrombocytopenia risks in ARDS COVID-19 patients treated with high-dose linezolid during vvECMO therapy: an observational study.

Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD.

Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation-A Step toward Correct Dosing.

During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO.

Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase.

Background: We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug events (ADEs).

Research Design And Methods: Case reports reported to VigiBase were accessed using Empirica™ Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used.

The effect of nasal douching by hypertonic 2.3 per cent sea water with algae extracts on the concentration of epidermal growth factor, transforming growth factor-α and interleukin-8 in nasal secretions of patients with nasal polyposis following endoscopic surgical treatment.

Objective: To investigate epidermal growth factor, transforming growth factor-α and interleukin-8 production in nasal mucosa irrigated with hypertonic 2.3 per cent solution with algae extracts, in comparison to 0.9 per cent NaCl during the first two weeks after surgery for nasal polyposis, in relation to symptoms and local findings.

Understanding hemoglobin contribution to high-dose methotrexate disposition-population pharmacokinetics in pediatric patients with hematological malignancies.

Purpose: The aim of the present study was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) and to describe the influence of variability factors.

Methods: The study included 50 patients of both sexes (aged 1-18 years) who received 3 or 5 g/m of HDMTX. A nonlinear mixed effect modeling approach was applied for data analysis.

The Influence of Subclinical Active Inflammation on IFX Pharmacokinetic Modeling and Disease Progression Assessment: Findings from a Prospective Real-World Study in Inflammatory Bowel Disease Patients.

Background And Aims: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.

Methods: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy.

Successful Caesarean Section on Ticagrelor Treatment One Day after Primary Percutaneous Coronary Intervention.

Caesarean section is a challenging intervention in patients treated with dual antiplatelet therapy. We present a case of a 32-year-old pregnant woman experiencing large acute myocardial infarction (MI) of the anterolateral wall, complicated by cardiogenic shock in the 38th week of pregnancy, and treated with drug-eluting stent implantation and dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor. Less than 24 h after the MI delivery started, an urgent Caesarean section was indicated.

Association of clozapine and norclozapine levels with patient and therapy characteristics-focus on interaction with valproic acid.

Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use.

Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients' data during routine TDM were collected retrospectively from clinical records.

Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes.

Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising.

Methotrexate concentrations and associated variability factors in high dose therapy of children with acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Monitoring and optimization procedures improved high dose methotrexate (HDMTX) treatment outcomes. However, there are still some concerns regarding unexplained concentration variability. The objective of this study was to evaluate drug concentrations and associated variability factors in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on HDMTX.

Drug-induced liver injury associated with the use of newer antiseizure medications in the elderly: an analysis of data from VigiBase.

Background: Data on drug-induced liver injury (DILI) caused by newer antiseizure medications (ASMs) in the elderly are scarce and mainly come from literature case reports. We analyzed Individual Case Safety Reports (ICSRs) of DILI in elderly patients treated with newer ASMs reported to VigiBase.

Research Design And Methods: Empirica™ Signal software was used to retrieve ICSRs reported to VigiBase up to 31 December 2021 and to calculate Empirical Bayesian Geometric Mean and corresponding 90% confidence intervals (EB05, EB95) for each drug-event pair.

Lidocaine clearance as pharmacokinetic parameter of metabolic hepatic activity in patients with impaired liver.

Background: The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value.

Methods: Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the intervention. LID was administered in single i.

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology.

Objective: Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations.

Review of the Clinical Pharmacokinetics, Efficacy and Safety of Pembrolizumab.

Background: Treatment of various types of cancer has been improved significantly with the discovery of biological drugs that act as immune checkpoint inhibitors (ICIs). Pembrolizumab is a humanized monoclonal anti- PD-1 antibody currently approved for the treatment of a wide range of tumors, with more indications still being investigated in ongoing clinical trials.

Objective: The aim of this paper is to present all currently available data regarding pembrolizumab pharmacokinetic and pharmacodynamic characteristics.

Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials.

Background: Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.

The impact of treatment choices on potential drug-drug interactions in hypertensive patients.

Aims: The aim of this study was to analyse potential drug-drug interactions (pDDIs) and their potential adverse drug reactions (ADRs) among hypertensive patients. Moreover, we investigated the possibility of reducing pDDIs with different treatment choices.

Methods: This was a cross-sectional study including all outpatients with hypertension and two or more medications, treated in a university hospital in Serbia.

Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina.

The COVID-19 pandemic exerted a profound impact on health systems worldwide. Moreover, significant concerns were raised in terms of middle- and long-term consequences of postponing care in non-COVID patients. The primary aim of the study was to describe the remote pharmaceutical care service (telepharmacy) during the COVID-19 pandemic in the Republic of Srpska (RS), Bosnia and Herzegovina.

Population exposure-response model of I in patients with benign thyroid disease.

Purpose: The study aimed to explore the relationship of different exposure measures with I therapy response in patients with benign thyroid disease, estimate the variability in the response, investigate possible covariates, and discuss dosing implications of the results.

Methods: A population exposure-response analysis was performed using nonlinear mixed-effects modelling. Data from 95 adult patients with benign thyroid disease were analysed.

Effects of extract vs roxithromycin on chemokine levels in nasal secretions of patients with uncomplicated acute rhinosinusitis.

Background: Previous investigations suggest the use of extract from the roots of (EPs 7630) for the therapy of uncomplicated rhinosinusitis. The aim of this prospective study was to compare the effects of herbal drug EPs 7630 and antibiotic roxithromycin on chemokine production in nasal mucosa and clinical parameters in patients with uncomplicated acute bacterial rhinosinusitis (ABRS).

Methods: Seventy-eight ABRS patients were divided into 26 patients receiving EPs 7630 tablets, 3 × 20 mg/day per os (group 1), 26 patients receiving roxithromycin tablets, 2 × 150 mg/day per os (group 2), both for 10 days, and 26 patients who received no therapy (Control group).

Outcomes of infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study.

Background: infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia.

A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention.

Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1. Pharmacokinetic (PK) data from study RMP-02/MTN-006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV-1 seronegative adults was used to construct a multicompartment plasma-rectal tissue population PK model for TFV and tenofovir-diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate).

Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis.

Background: The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic.