Ustav farmakologie

Olomouc, Czech Republic

Ustav farmakologie

Olomouc, Czech Republic
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Urbanek K.,Ustav farmakologie
Interni Medicina pro Praxi | Year: 2017

Infliximab is the first monoclonal antibody directed to TNFα. Used in the treatment of rheumatoid arthritis or other arthritis, inflammatory bowel diseases and psoriasis. Infliximab is administered by slow intravenous infusion, typically at doses of 3-5 mg / kg at intervals of 1-8 weeks. It is slowly eliminated from the body with a half-life of 7-12 days. For its high effectiveness and safety is a targeted first-line treatment of these diseases. Its side effects include especially infusion reactions and the risk of opportunistic infections, other adverse reactions are generally mild or infrequent.


Urbanek K.,Ustav farmakologie
Kardiologicka Revue | Year: 2017

Rivaroxaban is an oral selective, direct factor Xa inhibitor. It has well predictable pharmacodynamics and pharmacokinetics. Depending on the size of the dose, it inhibits thrombin formation after 24 hours. It does not block the existing thrombin activity and thus enables continued activation of endogenous anticoagulant factors. After oral administration it is well absorbed, its bioavailability varies between 80 and 100%. It is bound to plasma proteins in 92 to 95%, its average distribution volume is 50 litres. The main metabolising systems are cytochromes P450 3A4 and 2J2. It is excreted mainly via the kidneys; about one third of the administered amount being excreted unchanged, primarily by tubular secretion. The remaining two thirds are excreted as inactive metabolites in urine and bile. The median terminal half-life in younger individuals is 5–9 hours, and 11–13 hours in older individuals. Rivaroxaban pharmacokinetics is minimally affected by age or sex of the patient, and does not require dose adjustments in patients with extremely low or high or with mild-to-moderate renal or hepatic insufficiency. © 2017, Ambit Media a.s. All rights reserved.


With several high-profile biologics nearing the expiration of their patents, the focus is now on follow-up biologic products, also called biosimilars. This paper reviews the current European Union regulation of the biosimilar approval pathway, particularly in contrast to the traditional generic drug approval process. Using the example of biosimilar infliximab, the paper describes the main specific features of the development and characterization of biologics, including a current discussion on nomenclature and patient, physician information, and automatic substitution.


Cardiovascular illnesses belong to diseases with the highest prevalence. They are also the most predominant reason of death in the vast majority of European countries. Hence, the offer of effective treatment of these dis eases is absolutely crucial. This text focuses on the current therapeutical use of ivabradine in its approved indications - chronic stable angina pectoris and chronic heart failure - in the context of so far published relevant clinical trials.


Infliximab CT-P13 is the first monoclonal antibody that has been tested in accordance with the European Medicines Agency for biosimilars and also has been approved. The article summarizes the results of preclinical and clinical evaluation of this particular substance and its comparison with the original product.


Proprotein convertase subtilisin-kexin type 9 (PCSK9) is mainly responsible for the recycling receptors for LDL particles. This results in an increase in LDL levels, which then drastically contributes to the development of atherosclerotic changes in vessel wall. This increases cardiovascular morbidity and mortality. New drugs based on monoclonal antibodies as alirocumab or evolocumab belongs amo ng PCSK9 inhibitors. Their administration leads to a dramatic reduction in LDL particles up to 50-60 %. Given that the Czech Republic ranks among the countries with high cardiovascular mortality, is introduction of these new drugs in clinical practice one of the key milestones in the treatment of high blood lipid levels and improve this negative situation. © 2016, SOLEN s.r.o. All Rights Reserved.


The medicinal product Relvar Ellipta is a new dry powder inhaler containing a new fixed combination of the inhaled corticosteroid fluticasone furoate (FF) and the selective ultra-long-Acting, 2-Adrenergic agonist vilanterol. The article summarizes the most interesting data from the preclinical development and phase I clinical evaluation of both molecules. Among the modern inhaled corticosteroids, FF has the highest affinity towards the glucocorticoid receptor. In preclinical testing in vitro and in vivo, the glucocorticoid activity of FF was stronger and it had longer duration than that of fluticasone propionate. The inhaled particles of FF dissolve very slowly bringing two major advantages. First, the pulmonary residence time is two-fold longer than that of fluticasone propionate making a once-daily inhalation possible and, second, the slower rate of absorption results in very low concentrations of FF in the blood. The safety profile of FF is further supported with the high velocity of hepatic elimination, biotransformation to inactive metabolites, negligible oral bioavailability and extensive binding to plasma proteins. Preclinical and clinical evaluation of vilanterol was able to document its improved pharmacodynamic characteristics in comparison to salmeterol. Namely, the intrinsic activity of vilanterol is higher and its effect has a more rapid onset and a longer duration. Both the extraordinary 2-selectivity and appropriate pharmacokinetic characteristics (fast hepatic elimination, conversion to inactive metabolites, short half-life, minimal oral bioavailability) are responsible for a favorable safety profile of vilanterol. The duration of action over 24 h following inhalation is ascribed to the high-Afinity binding of vilanterol to specific binding sites on the 2-receptor which enables its retention nearby and a repeated interaction with the receptors active site.


Bultas J.,Ustav Farmakologie
Casopis Lekaru Ceskych | Year: 2015

Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - acute mountain sickness - is mainly characterized by subjective symptoms (headache, loss of appetite, insomnia, weakness, nausea and rarely also vomiting). Advanced and life-threatening forms are characterized by tissue edema - cerebral or pulmonary high altitude edema. The common denominator of these acute forms is the low oxygen tension leading to hypoxemia and tissue ischemia. Sum of maladaptive or adaptive processes can modify the clinical picture. Underlying mechanisms of the chronic forms of pulmonary disease are the adaptation processes - pulmonary hypertension and polycythemia leading to heart failure. The only causal therapeutic intervention is to restore adequate oxygen tension, descend to lower altitudes or oxygen therapy. Pharmacotherapy has only a supportive effect. The prophylaxis includes stimulation of the respiratory center by carbonic anhydrase inhibitors (acetazolamide) antiedematous treatment with glucocorticoids (dexamethasone), increase lymphatic drainage of the lungs and brain by β2-agonists (salmeterol) or mitigation of pulmonary hypertension by calcium channel blockers or phosphodiesterase-5 inhibitors (sildenafil or tadalafil).


An advent of each new group of drugs associated with big expectations is inevitably followed by a period of critical evaluation. From the perspective of a gastroenterologist, a higher incidence of bleeding in the gastrointestinal tract associated with the use of some of the novel oral anticoagulants in comparison with warfarin is somewhat disappointing. Increased incidence of gastrointestinal haemorrhagic events was observed in both direct thrombin inhibitor - dabigatran, as well as some direct factor Xa inhibitors - xabans, specifically in rivaroxaban and edoxaban. In phase III clinical studies, the meta-analyses and analyses of registers has observed a relative increase in all bleeding events as well as major bleeding into the gastrointestinal tract of about a quarter to a half, but in absolute values the increase in the incidence is on average low, only 0.3%. However, for the individual drugs the absolute increase may be greater, e.g. in the case of rivaroxaban 1%. Given the fact that there are significant differences amongst individuals, rivaroxaban and dabigatran (at a dose of 2 × 150 mg) have a higher risk and the therapy with apixaban is not associated with a higher incidence of gastrointestinal bleeding, it is advisable for people at high risk of gastrointestinal bleeding to choose apixaban as the optimal anticoagulation therapy. The incidence of bleeding in the gastrointestinal tract is growing for a number of reasons, which increase the exposure to different drugs. These factors include in particular drug and food interactions, decreased renal functions, lower weight and some pharmacogenetic factors. Independently of the level of anticoagulants, the risk of gastrointestinal bleeding increases also the use of non-steroidal (even steroidal) anti-inflammatory drugs, infection with Helicobacter pylori or e.g. diverticulosis.


Direct oral anticoagulants (DOACs) are agents that have recently been introduced into clinical practice to replace warfarin. In addition to improved efficacy and safety, one of the anticipated benefits was the absence of the need for regular monitoring of coagulation parameters with the necessity of adjusting the doses on the basis of the obtained results. However, increasing need for quantitative determination of these substances in plasma in specific cases has been found. The gold standard for the essay of DOACs’ plasma concentrations is the LC-MS method. In daily practice, the use of indirect methods such as dTT for inhibitors of thrombin and chromogenic determination of anti-Xa for factor Xa inhibitors is more usual. So far, it has not been recommended for any DOAC that therapeutic drug monitoring should be performed repeatedly for dosage adjustment. Plasma concentrations measurements are used in cases such as suspected noncompliance, bleeding complications during treatment, the need for acute thrombolysis or surgical procedures. © 2015, Ambit Media a.s. All rights reserved.

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