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. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Data sources: Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. Data summary: There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Conclusion: Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.

Background/Objectives: 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. Methods: We included 61 UC and 45 CD patients. Patients’ data and trough VDZ concentrations were retrospectively obtained. Population PK analysis was performed using non-linear mixed-effects modelling with NONMEM (version 7.5). Graphs and statistical analyses were performed using R (version 4.1.3). Results: In total, 116 trough VDZ concentrations from 106 patients were described by a two-compartment model. For a typical patient, clearance (CL) was estimated at 0.159 L/day, while in patients previously treated with anti-TNFα agents, VDZ CL increased by 26.4% on average. In univariate binary logistic regression, VDZ trough concentration was not statistically significant predictor of remission, whereas CL was. Moreover, combined CL and faecal calprotectin (FCP) were a statistically significant predictors of remission. The hazard ratio (HR) for CL above 0.1886 L/day was 0.35 (p = 0.05) and for FCP below 250 µg/g was 2.66 (p = 0.02) in a time-to-event analysis. Conclusions: Our population PK model incorporates the effect of prior anti-TNFα agents on CL, suggesting its association with more severe forms of IBD. VDZ CL emerged as a more robust and clinically relevant predictor of remission in IBD patients than trough concentration.

Background/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. Methods: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center “Zvezdara”, Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration–time profiles based on 24 covariate combinations specified within the models. Results: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto et al. fulfilled the evaluation criteria. Simulation analysis further demonstrated that the median VDZ concentration remains above 12 μg/mL at week 22 during maintenance treatment for approximately 45–60% of patients with the best-case covariate combinations and an 8-week dosing frequency. Conclusions: None of the published models satisfied the combined criteria (MDPE, MAPE, percentages of prediction error within ±20% and ±30%), rendering them unsuitable for a priori predictions. However, two models demonstrated better suitability for simulation-based applications.

The application assessment of different programs was performed with equivalence tests for method transfer pro second-order derivative spectrophotometry. The digital second-order derivative spectra were calculated on different instruments; GBC Scientific Equipment Cintra 20 (Cintral v.2.6 and Spectral v.1.70 software programs) and Thermo Scientific Evolution 300 (VISIONPro software) were analyzed using the amplitude A/B ratio (A = ² D _265,263 ; B = ² D _263,261 ). Amplitude A/B ratio is the resolution parameter for derivative spectrophotometry prescribed in European Pharmacopoeia. The obtained values for A/B ratio were either very similar or significantly different among programs: 0.669 (Cintral v.2.6), 0.549 (Spectral v.1.70), 0.556 (medium indirect VISIONPro), 0.557 (one-step Savitzky–Golay 7 VISIONPro), 0.689 (two-step Savitzky–Golay 7 VISIONPro). Method transfer was possible between Spectral v.1.70 and VISIONPro (medium indirect and one-step Savitzky–Golay 7), but the values obtained in Cintral v.2.6 were not comparable to the other programs. The absorbance data exported from both instruments were additionally calculated in OriginPro8 which provided almost the same mean A/B values (0.627 Cintral v.2.6; 0.624 VISIONPro), confirming that the two instruments recorded the same zero-order spectra. The calculation of resolution parameter could be used for verification of program comparison, which would enable transfer between sender and receiver laboratory. The accordance between program algorithms was confirmed when acceptable differences for values of resolution parameter (A/B ratios) were achieved.

Background/Objectives: Mucosal healing (MH) is a key therapeutic target in inflammatory bowel disease (IBD) associated with sustained remission, reduced hospitalisation, and improved outcomes. Its assessment relies on endoscopic evaluation, which is invasive, costly, and not always feasible. Therapeutic drug monitoring (TDM) of infliximab (IFX) and evaluation of available biomarkers may provide non-invasive tools for predicting treatment response. This study investigated the association between IFX pharmacokinetics, routinely available blood biomarkers and MH to identify potential surrogates for predicting treatment outcomes. Methods: A monocentric, retrospective, real-world study was conducted, and pharmacokinetic analysis was performed in NONMEM version 7.5, applying a model with priors to estimate individual pharmacokinetic parameters. Endoscopic findings were collected, and patients were categorised according to achievement of MH. Univariate and multivariable logistic regression analyses were performed to evaluate the predictive value of tested variables, and receiver operating characteristic (ROC) curve analysis was performed to assess discriminative performance. Results: All evaluated variables demonstrated statistically significant associations with MH (p < 0.05). IFX clearance showed a strong inverse relationship with the probability of achieving MH. Leukocyte count exhibited particularly good discriminative ability, with an area under the ROC curve of 74.04% and an odds ratio of 0.78, highlighting its potential clinical utility. Multivariable logistic regression identified a model including IFX clearance and platelet count (PLT) as the most promising predictors of MH. Significant differences between patient subgroups indicated the association of higher PLT and modestly increased IFX clearance with a lower probability of MH. Conclusions: IFX clearance represents a promising surrogate marker for MH. TDM-derived parameters coupled with routinely available biomarkers may improve treatment response assessment. Combining pharmacokinetic and biomarker-based approaches could reduce reliance on repeated endoscopies while facilitating more effective IBD monitoring in clinical practice.

Pharmacists, as the most accessible healthcare professionals, play a key role in supporting mental health. Recognition of the importance of their active involvement in treating patients with anxiety disorders is increasing. This study aimed to examine pharmacists' attitudes and perceptions regarding the provision of pharmaceutical care to patients with anxiety. Data were collected using a specially designed questionnaire adapted from related studies. Statistical analysis was performed in Microsoft Excel and SPSS Statistics. Survey reliability was confirmed with Cronbach's Alpha (a = 0.892). Associations between respondents' characteristics (gender, work experience, education level) and scores on individual survey items were analyzed using the Mann-Whitney U and Kruskal-Wallis test. The sample consisted of 104 women and 17 men, with a mean age of 38.16 ± 10.86 years and a mean work experience of 12.24 ± 10.72 years. Most work in community pharmacies (91.74%) and lack postgraduate education (85.12%). The majority reported regularly advising patients on the appropriate use of medication (57.02% always; 27.27% often) and on the risks of self-discontinuing therapy (43.8% always; 31.4% frequently). In addition, 56.2% always refer patients to a physician when necessary, while fewer personally contact physicians (9.92% never; 23.97% rarely). About 23% seldom conduct patient follow-up, and roughly 20% do not routinely check for contraindications. Pharmacists with 11-15 years of experience were significantly more willing to contact physicians than those with 1-5 years of experience, while no difference was observed in the other groups (6-11, 16-20, >20 years). Results indicate that neither gender nor education level significantly influences pharmacists' professional activities. The effect of work experience observed in specific subgroups warrants further investigation to determine whether it reflects a genuine need for additional support of younger pharmacists.