Eur J Pharm Biopharm
December 2024
Background: Bioequivalence risk assessment as an extension of quality risk management lacks examples of quantitative approaches to risk assessment at an early stage of generic drug development. The aim of our study was to develop a model-based approach for bioequivalence risk assessment that uses pharmacokinetic and physicochemical characteristics of drugs as predictors and would standardize the first step of risk assessment.
Methods: The Sandoz in-house bioequivalence database of 128 bioequivalence studies with poorly soluble drugs (23.
Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion.
View Article and Find Full Text PDFOxidative stress resulting from a disturbance of the endogenous redox system is suspected in numerous diseases of the central nervous system, including epilepsy. In addition, antiseizure medications (ASMs), especially those of the old generation, may further increase oxidative stress. To evaluate the effects of ASM generation on oxidative stress, we conducted a cross-sectional study in patients with epilepsy treated with old, new, and polytherapy.
View Article and Find Full Text PDFBackground: The antiepileptic drug lamotrigine (LTG) shows high pharmacokinetic variability due to genotype influence and concomitant use of glucuronidation inducers and inhibitors, both of which may be frequently taken by elderly patients. Our goal was to develop a reliable quantification method for lamotrigine and its main glucuronide metabolite lamotrigine-N2-glucuronide (LTG-N2-GLU) in dried blood spots (DBS) to enable routine therapeutic drug monitoring and to identify altered metabolic activity for early detection of drug interactions possibly leading to suboptimal drug response.
Results: The analytical method was validated in terms of selectivity, accuracy, precision, matrix effects, haematocrit, blood spot volume influence, and stability.
Administration of monoclonal antibodies (mAbs) is currently focused on subcutaneous injection associated with increased patient adherence and reduced treatment cost, leading to sustainable healthcare. The main bottleneck is low volume that can be injected, requiring highly concentrated mAb solutions. The latter results in increased solution viscosity with pronounced mAb aggregation propensity because of intensive protein-protein interactions.
View Article and Find Full Text PDFPsychotropic prescription drugs are commonly involved in intoxication events. The study's aim was to determine a comparative risk for intoxication in relation to prescribing rates for individual drugs. This was a nationwide observational study in Slovenian adults between 2015 and 2021.
View Article and Find Full Text PDFThe aim of this study was to externally validate the predictive performance of published population pharmacokinetic models of gentamicin in all paediatric age groups, from preterm newborns to adolescents. We first selected published population pharmacokinetic models of gentamicin developed in the paediatric population with a wide age range. The parameters of the literature models were then re-estimated using the PRIOR subroutine in NONMEM.
View Article and Find Full Text PDFBackground And Objectives: Risk assessment related to bioequivalence study outcome is critical for effective planning from the early stage of drug product development. The objective of this research was to evaluate the associations between solubility and acido-basic parameters of an active pharmaceutical ingredient (API), study conditions and bioequivalence outcome.
Methods: We retrospectively analyzed 128 bioequivalence studies of immediate-release products with 26 different APIs.
Background And Objectives: Understanding predictive potential of parameters to perform early bioequivalence (BE) risk assessment is crucial for good planning and risk mitigation during product development. The objective of the present study was to evaluate predictive potential of various biopharmaceutical and pharmacokinetic parameters on the outcome of BE study.
Methods: Retrospective analysis was performed on 198 Sandoz (Lek Pharmaceuticals d.
: Patients with schizophrenia are often exposed to polypharmacotherapy, which may lead to drug-drug interactions. The aim of the study was to investigate the prevalence of potential drug-drug interactions (pDDIs) in hospitalized patients with schizophrenia spectrum disorders and to identify factors associated with pDDIs and manifested symptoms and signs. : This cross-sectional observational study included 311 inpatients admitted to a psychiatric hospital.
View Article and Find Full Text PDFComprehensive comparisons of similar lipid based drug delivery systems produced by different technologies are scarce. Spray drying and fluid bed layering technologies were compared with respect to the process and product characteristics of otherwise similar simvastatin loaded dry emulsion systems. Fluid bed layering provided higher process yield (83.
View Article and Find Full Text PDFObjective: The purpose of this paper is to present the use of Design of Experiments and multivariate analysis for evaluation of a modified-release drug product stability to support post-approval lean stability approaches. The focus of the paper was to investigate potential root-causes for acceleration of dissolution upon stability.
Methods: For statistical evaluation of stability data, multiple linear regression statistics was used.
Ustekinumab is a monoclonal antibody used in Crohn's disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic-pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens.
View Article and Find Full Text PDFObjectives: Some patients with Crohn's disease do not achieve remission with the approved maintenance dosing of ustekinumab every 8 weeks, possibly due to insufficient drug exposure. We aimed to study the exposure-response relationship for endoscopic remission and biomarker normalization with ustekinumab dose escalation to every 4 weeks.
Methods: Out of 135 consecutive patients, 44 with active Crohn's disease despite standard maintenance dosing [at least one of C-reactive protein (CRP) >5 mg/L, fecal calprotectin >100 mg/kg, simple endoscopic score (SES) for Crohn's disease >3] underwent dose escalation to every 4 weeks.
Monoclonal antibodies (mAbs) have been extensively developed over the past few years, for the treatment of various inflammatory diseases. They are large molecules characterized by complex pharmacokinetic and pharmacodynamic properties. Therapeutic drug monitoring (TDM) is routinely implemented in the therapy with mAbs, to monitor patients' treatment response and to further guide dose adjustments.
View Article and Find Full Text PDFDodeca-2,4,8,10/-tetraenoic isobutylamide (tetraene) is the main component of DC. lipophilic extract, the bioavailability and immunomodulatory effect after oral administration in soft gel capsules in healthy volunteers of which we have already demonstrated. In the present work, we assessed the transdermal administration as an alternative route of administration of such an alkamide.
View Article and Find Full Text PDFThe objective of this study was to assess the possibility of applying Partial Least Squares (PLS) statistics with the use of experimental design approach towards stability evaluation of the Saxagliptin drug product. The influences of temperature, time, dose, packaging, batch, and oxygen protection were analyzed for identification of critical factors responsible for degradation of saxagliptin and prediction of impurity levels at various storage conditions. Predicted levels of the impurity DP-2 were lower for at least 0.
View Article and Find Full Text PDFDietary intake is the predominant route of human exposure to bisphenol A and one of the important food commodities is milk. The aim of our study was to preliminarily evaluate the bisphenol A exposure and disposition in sheep milk after repeated dietary and subcutaneous administration of a relatively low dose (100 µg/kg of b. w.
View Article and Find Full Text PDFBackground & Aims: Little is known about the relationship between ustekinumab exposure during the first 2 weeks of treatment and outcomes of patients with Crohn's disease (CD). We investigated the relationship between serum concentrations of ustekinumab during the first 2 weeks of treatment and endoscopic and biochemical remission in patients with CD.
Methods: In a prospective observational study, we measured concentrations of ustekinumab in serum samples from 41 consecutive patients who started treatment with ustekinumab (approximately 6 mg/kg, intravenously, then 90 mg every 8 weeks), due to endoscopic markers of active CD, at a single center from October 2017 through January 2019.
Purpose: The aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam.
Methods: In the study were included 49 critically ill children of both genders (from 0 to 130 weeks of age) with severe acute bronchiolitis hospitalised in intensive care units. Nonlinear mixed effects modelling approach was applied for data analyses and simulations.
Background And Objective: Echinacea angustifolia DC. and Zingiber officinale Roscoe are two natural products with documented immunomodulatory activity, both able to modulate the expression of important immune-related genes. Thus, their use in combination seems to be particularly promising.
View Article and Find Full Text PDFA simple, fast, and cost-effective LC-MS/MS method for quantification of rifampicin in human plasma was developed and fully validated. The plasma samples containing rifampicin and isotopically labelled internal standard rifampicin D8, were cleaned up using a Captiva ND Lipids filtration plate. Chromatographic separation was achieved on an 1290 Infinity liquid chromatograph coupled to 6460 Triple Quadrupole operated in positive mode on a core-shell Kinetex C18 column (50 × 2.
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