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.

Due to frequent clinical trial failures and consequently fewer new drug approvals, the need for improvement in drug development has, to a certain extent, been met using model-based drug development. Pharmacometrics is a part of pharmacology that quantifies drug behaviour, treatment response and disease progression based on different models (pharmacokinetic - PK, pharmacodynamic - PD, PK/PD models, etc.) and simulations. Regulatory bodies (European Medicines Agency, Food and Drug Administration) encourage the use of modelling and simulations to facilitate decision-making throughout all drug development phases. Moreover, the identification of factors that contribute to variability provides a basis for dose individualisation in routine clinical practice. This review summarises current knowledge regarding the application of pharmacometrics in drug development and clinical practice with emphasis on the population modelling approach.

Background: Treatment of various types of cancer has been improved significantly with the discovery of biologic 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. Also, the possibility of using predicative biomarkers to monitor patients during cancer treatment is discussed. Methods: Database research was carried out (PubMed, ScienceDirect). Information was gathered from original articles, the European Medicines Agency datasheets and results from clinical trials. Results: This review summarizes present-day knowledge about the pharmacokinetics, different modeling approaches and dosage regimens, efficacy and safety of pembrolizumab and therapeutic monitoring of disease progression. Conclusion: This review points out consistent pharmacokinetic characteristics of pembrolizumab in various cancer patients, the lack of pharmacokinetic-pharmacodynamic/outcome relationships, the need of adequate biomarkers predicting treatment success. Hence, there is a clear necessity for more data and experience in order to optimize pembrolizumab treatment for each individual patient.

Background Vedolizumab (VDZ) is recommended for induction of remissionin patients with inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) based on pharmacokinetic measurements of VDZ trough plasma concentrations adds-up on routine patients’ clinical follow-up. Great interpatient variability in VDZ serum concentrations is observed. Our aim was to investigate factors contributing to variations in VDZ levels by developing population pharmacokinetic model based on sparse TDM data, and understand its importance in reaching adequate response. Methods Retrospective data from IBD patients undergoing treatment with VDZ were reviewed, and patients with measured VDZ serum concentration were included in analysis. In addition, demographic, therapy and clinical characteristics were collected; including various inflammatory biomarkers such as platelets, leucocytes, C-reactive protein, sedimentation rate, fecal calprotectin, etc., and calculated Mayo, SES scores, where appropriate. VDZ dose of 300 mg was administered as 30-minutes infusion at week: 0, 2 and 6 during induction, with a 4-, 6- or 8-week dosing interval during maintenance phase. Population modeling approach was applied to characterize pharmacokinetic profile of VDZ. In addition, logistic analysis was implemented to test correlation among VDZ concentration, disease biomarkers, and appropriate clinical scores. Results In total, 115 VDZ trough concentrations obtained from 107 patients were analysed. Patients’ characteristics are given in Table 1. VDZ concentrations were described by two-compartment model. Estimated typical value of VDZ clearance (CL) was 0.226 L/day, without any difference among ulcerative colitis (UC) and Crohn’s disease (CD) patients. We identified that previous treatment with anti-TNF biologics increases CL by on average 24.8%. In addition, our preliminary analyses indicate higher probability of thrombocytosis with lower VDZ levels. Median VDZ concentration in patients whose platelets were above and below 350 (109/L) were 15.33 and 20.29 microg/mL, respectively (Figure 1). Conclusion Our preliminary results suggest that platelets account as inflammation burden marker and previous antiTNF treatment may be predictive factors for proactive VDZ optimization.

Thyroid dysfunction is one of the most prevalent endocrine disorders, especially common in female patients. If patients are not diagnosed in time or adequately treated, the patients' quality of life can be significantly impaired and additional health problems may occur, considering the key roles of thyroid hormones in the body. Therefore, it is necessary to raise awareness about the importance of recognition of symptoms that may indicate a potential problem with the thyroid gland and help to identify possible causes. For patients who are already being treated with levothyroxine (hypothyroidism), or thiamazole, carbimazole or propylthiouracil (hyperthyroidism), it is necessary to point out the necessity of proper, regular use of the drugs and implementation of accompanying nonpharmacological measures, as well as the potential for the occurrence of adverse reactions and interactions with other drugs or food. A significant role in the mentioned activities should be played by the pharmacist, as the most accessible member of the health team, who can, if necessary, refer the patient to a doctor for diagnosis, monitor the effectiveness and safety of the therapy, and provide appropriate patient counseling.