Klinické hodnocení léčiv

Věra Strnadová

Klin Farmakol Farm. 2007;21(3):95  

The importance of dosage intervals for the therapy using time-dependent antibiotics: Examples of therapeutic drug monitoring

Josef Šedivý, Anna Jedličková, Olga Černá

Klin Farmakol Farm. 2007;21(3):98-102  

Based on growth/killing microbial parameters in vitro and individual drug concentration/time fluctuations, the rate of bactericidal effect of two time-dependent antibiotics, vancomycin and amoxicillin/clavulanate, was calculated to optimize the next therapy. Predicted time to decrease the number of viable bacteria to 10–6 (as compared with the start of therapy) was adopted as surrogate criterion of the bactericidal effect. Even of highly susceptible strains, microbial killing activity of time-dependent antibiotic agent ceases when its concentration declines under about 4 times the MIC-level. It takes place mainly at the end of too long intermittent...

Thaliomide - new comeback

Miloš Jeseňák, MUDr. Zuzana Lietavová, MUDr. Alena Szökeová, MUDr. Peter Lietava, MUDr. Ivana Plameňová, MUDr. Miloš Mráz, Mgr. Eva Babušíková PhD, Ján Buchanec, prof. MUDr. Peter Bánovčin CSc

Klin Farmakol Farm. 2007;21(3):128-132  

Thalidomide (THD) has been recently introduced into therapeutical algorithms of many diseases (especially oncological and inflammatory) with poor response to standard therapy. The characteristic effect of THD is immunomodulatory, anti-inflammatory, antirheumatic, antiangiogenic, antitumorous and virostatic. The main known mechanism of THD is inhibition of TNF-α system, correction of disbalance in cytokine net, stimulation of TH2 cells and inhibition of TH1 cells, increase of cytotoxicity of NK cells and changes in the profile of adhesive and communication molecules on the surfaces of various cells (blood cells, endothelium, tumour cells). The...

Clinical significance of cytochrome P4502D6

Jana Ďuricová, Milan Grundmann

Klin Farmakol Farm. 2007;21(3):133-136  

The enzymes of the cytochrome P450 are the major enzymes responsible for metabolizing of drugs. The CYP2D6 is highly polymorphic enzyme and shows a very high degree of interindividual variability. The CYP2D6 metabolizes approximately 25 % of all medications. Many studies point out the significant influence of CYP2D6 on pharmacokinetics and pharmacodynamics of drugs.

Drugs and pregnancy

Ivana Kacířová, Milan Grundmann

Klin Farmakol Farm. 2007;21(3):137-143  

Epidemiologic surveys show that most of pregnant women use at least one medication during pregnancy. Several factors determine whether a drug is teratogenic, including the gestational timing of the exposure, as well as the dose, route and nature of the drug itself. The complex physiologic unit of mother, placenta and fetus undergoes considerable dynamic physiologic changes during pregnancy. Therapeutic drug monitoring during pregnancy aims to better individualize dosing regimens of pregnant women.

Risk management system and drug safety examples

Jozef Kolář, Milan Kriška

Klin Farmakol Farm. 2007;21(3):145-150  

A risk management system is a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products, including the assessment of the effectiveness of those interventions. The prescription and distribution of some drugs are subject to restrictions and limitations. The authors describe several the most famous programs like TOUCH (natalizumab, Tysabri), S.T.E.P.S. a PRMP (thalidomide, Thalomid), RevAssist (lenalidomide, Revlimid), SMART, iPLEDGE (isotretinoin, Accutane), CPMS (clozapine, Clozaril), T.I.P.S. (dofetilide, Tykosin). Particular attention is paid to the systems alert...

Current options and new perspectives of systemic therapy of breast cancer

Luboš Petruželka

Klin Farmakol Farm. 2007;21(3):103-113  

Breast cancer is a clinically heterogeneous disease, and existing histological classifications do not fully capture the varied clinical course of this disease. Reverse transcription polymerase chain reaction and DNA microarrays led to novel risk stratification methods and to new molecular classification of breast cancer. There are many approaches to the treatment of metastatic breast cancer, including chemotherapy agents, endocrine therapies and newer targeted drugs (trastuzumab, bevacizumab and lapatinib). One of the most exciting developments of the past 2 decades has been the demonstration of improved disease-free and overall survival for the addition...

Hormonal regulations and possibilities of intervention in prostate cancer treatment

Kamil Belej, Ondřej Kaplan

Klin Farmakol Farm. 2007;21(3):114-118  

Since pivotal studies in 40´s of 20th century, hormonal therapy become the mainstay for the management of patiens with locally advanced and metastatic prostate cancer. In recent years, however, there has been an evolution towards increasing hormonal treatment of younger men with lower stage of disease or recurrent disease after definitive treatment. It is frequently used as a part of a multimodality approach.

What is discussed relate to clinical trials

Věra Strnadová

Klin Farmakol Farm. 2007;21(3):119-121  

The article points some often discussed issues of clinical trials out. It is mentioned ethical aspects, good clinical practice, drug clinical trials in minors and postgraduate education in this field. ICH-GCP definition of clinical trials indicates that sponzor of any clinical experiments with new drugs can be a pharmaceutical producer as well as university or investigator himself. This fact complicates the handle of some part of academic research that should be conducted according to GCP. Some examples of widely discussed clinical trial problems e. g. harmonisation versus unification, change in view on pediatric studies, main ethical aspects of clinical...

Co-operation of the investigator with the sponsor in clinical trials

Darina Hrdličková

Klin Farmakol Farm. 2007;21(3):122-124  

The investigator plays a key role in clinical trials both in case the trial is conducted by the sponsor – pharmaceutical company, or by a Contract Research Organisation. According to the Good Clinical Practice (GCP) the investigator is the person responsible for the clinical trial on the respective trial site. The physician in a role of an investigator has not only the rigt to conduct the trial, but also many trial related duties. In this article the duties are being described according to the time course of a clinical trial, inlcuding referring to relevant legislation. In the beginning of the co-operation related to a clinical trial the physician...

Medical ethics in the context of clinical research

Marta Munzarová

Klin Farmakol Farm. 2007;21(3):125-127  

The evolution of medical ethics from the very beginning to the present time with the special interest to clinical research and clinical trials is presented. The principles of medical ethics connected with dignity and wholeness of man are emphasized with respect to the special vulnerability of patients in times of moral relativism, utilitarianism and extreme admiration to scientific progress. The Nuremberg code is presented and some modern important international documents are mentioned. The attention is paid to some aspects of informed consent, to the work of ethical committee and first of all to the personality of physician – research worker...