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Clinical Oncology

FEBRUARY 10, 2018

[The role of early clinical studies in oncology]


[Although the basic theory of the early development of different drug groups is identical, due to their various pharmacological characteristics the design of the studies, the starting safe dose and the selection of the pharmacologic and therapeutic end-points show signifi cant differences. The development process of drugs is usually divided into two functionally different parts, the learning and the confi rming phases, respectively. The aim of the fi rst part is the description of the suggested targets, the mechanism of action in humans and the characterization of the drug-linked biomarkers. This section contains the microdose (phase 0), phase I and II studies. The end-point of this part is the proof of the underlying concept which was developed on the basis of the non-clinical studies. According to the internationally accepted terminology, this strategically important point is called the Proof of Concept (POC). Upon POC it has to be decided whether the drug-candidate possesses those qualities which make it worthwhile to perform human phase III studies, treating the statistically required number of patients for proving the good therapeutic effi cacy and safety of the drug. This section of the drug development is called the confi rmatory phase. The use of highly sophisticated technology opened the possibility to apply microdoses in humans for studying the pharmacokinetics and pharmacodynamics of new drugs as well as the characteristics of human biomarkers at very low, harmless drug doses. This approach made possible to draw important conclusions on the usefulness of biomarkers for the clinical practice even following the fi rst drug-application. The planning of phases I and II studies, the calculation of the applicable doses, the selection of the pharmacologic and therapeutic end-points, the use of biomarkers, are all based on the concept of translational medicine and are essentially dependent on the results obtained both in animal experiments and human microdose studies.]

Clinical Oncology

SEPTEMBER 15, 2016

[Obesity and cancer]


[The role of obesity in the development of cancer is well-known from ages. However, these days we witness the explosion-like increase of obesity, globally, but mainly in the economically advanced population, and, which is even more alarming, among youngsters. The prognosis of the obesity-related cancer is rather poor, therefore, the prevention, including the screening, have outstanding importance. Unfortunately, the participation of the obes persons, especially obes women, in these programs is very low. The diagnostics and therapies should consider the special features of obesity, which are related to the magnitude, distribution, composition of fatty tissue connected to the changes in pharmacokinetics. Moreover, the problems might be complicated with obesity-associated non-tumorous severe diseases (e.g. cardiovascular, diabetes type 2).This review covers different aspects of obesity-cancer relationships, with an emphasis on everyday oncology.]

Lege Artis Medicinae

JUNE 01, 2015

[Role of roflumilast in chronic obstructive lung disease]

NAGY László Béla

[The phosphodiesterase 4 inhibitor roflumilast supresses the function of a range of inflammatory cells and mediators contributing in the pathogenesis of chronic obstructive lung disease (COPD). This article reviews the current status of roflumilast, focusing on the pharmacokinetics, efficacy and safety. Phase III clinical trials have demonstrated that roflumilast reduces exacerbation frequency with accompanying improvements in lung function. This effect appeared to be the greatest in the phenotypes of patients who have frequent acute exacerbations, or/and whose characteristic feature is chronic bronchitis. It can presumably also reduce systemic inflammation. Such effect has not been documented in COPD yet. It is generally well tolerated, but the most common adverse effects include diarrhea, nausea, and headaches. Roflumilast is a promising drug as a supplementary therapy when symptoms are not adequately controlled by conventional COPD therapy.]

Clinical Neuroscience

SEPTEMBER 23, 2011

[New antiepileptic drugs, and therapeutic considerations]


[Epilepsy is not a singular disease, but a variety of disorders. It is affects up to 0.5% of the population. Over the past decade, the researchers have been made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced for the medication. The retigabine is a carbamic derivate, and the anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. The lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. The eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appears to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it must take some new approaches into consideration, in the therapeutic algorithm.]

Lege Artis Medicinae

FEBRUARY 21, 2004



[During the 40 year history of quinolones, from the first compounds (nalidixic acid, oxolinic acid, norfloxacin) suitable only for the treatment of mild urinary tract infections, an important group of antimicrobials was developed that can be used for the treatment of serious Gramnegative (ciprofloxacin, ofloxacin) and Grampositive (levofloxacin, moxifloxacin) infections. With the changes in the antimicrobial spectrum of the new derivatives it seems, that the clinical indications of the mainly anti-Gram-positive and the mainly anti-Gram-negative fluoroquinolones can be separated. We also learned the characteristics of their antibacterial activity that makes the optimal administration possible assuring the maximum clinical efficacy and the minimal development of bacterial resistance. The activity of fluoroquinolones can also be compromised by bacterial resistance so to preserve their clinical value it is important to follow the above mentioned principles in their use.]

Lege Artis Medicinae

NOVEMBER 10, 2008



[Medicinal preparations with durable analgetic effect are essential for therapy of the chronic pain. Controlling drug release allows the influence of fate of drug in the body as well as prolongation of duration of action. Development of innovative dosage forms as drug delivery systems offers increased efficacy and tolerability to improve patient's quality of life. Beside maintaining continuous therapeutical effect, extended drug release allows the spacing of dosing frequency. In addition, the more advantageous dosage regimen may improve the patient compliance during drug therapy. The review focuses on the aspects required to design drug carrier systems with original pharmacokinetic profile based on special pharmaceutical technological methods in order to optimize drug therapy for pain management.]

Clinical Neuroscience

MARCH 20, 2011

[Epilepsy in the elderly]

NIKL János

[The incidence of epilepsy is higher among the elderly, the most rapidly growing segment of the population, than in any other age group. New-onset seizures in elderly patients are typically symptomatic or cryptogenic partial seizures that require long-term treatment. Epilepsy in the elderly is a frequently occuring pathology, differing in etiology, clinical presentation and prognosis from those of young people. Establishing the diagnosis of epilepsy in old age can be more difficult than in younger patients due to the extensive range of differential diagnoses and a higher prevalence of concomitant disease. Beyond a certain age physiological and pathophysiological changes can affect the pharmacokinetics and pharmacodynamics of antiepileptic drugs(AEDs), increasing the risk of pharmacological interactions due to polypharmacy. Furthermore, the elderly people are sensitive to advers events of AEDs, as for example, to cognitive disturbances, osteoporosis. Several of newer AEDs have good safety and cognitive effect profiles and have no interactions with other drugs. The treatment strategies are demanding: they must take into consideration the co-morbidity, co-medication, alterations in drug metabolism, and the effects on aging body. These factors make the management of epilepsy in the elderly particulary challenging, but with appropiate pharmacological treatment most elderly people with epilepsy will remain seizurefree.]

Lege Artis Medicinae

JULY 20, 2005



[The author demonstrates the relationship between the innovative and generic antiepileptic drugs regarding the clinical aspects. Among the requirements for the registration of generics one can find small differences in the prescribed and the practical levels of bioequivalence. An important but not widely known fact is that these differences can lead to clinically important alterations if the effects of different generics or the effects on high risk patients are compared. While the increasing market of generics is due to economical factors (and rarely due to medical decisions), the safety of the drugs becomes extremely important. From this aspect, special patient populations eg. children, elderly people or patients with multiple illnesses under multidrug treatment are necessarily of greater medical importance. The characteristics of the antiepileptic drugs on the elderly patients, their increased sensitivity to particular adverse events and the possible somatic side effects are discussed in details. The type of epilepsy also has its special characteristics and is important in the choice of the most successful medicine. The development of the antiepileptic drugs shows a positive direction for their efficacy. In the discussion the author points out three main ways for using generic drugs: prescription of generic drug in monotherapy or as an additive in newly diagnosed patients, the exchange of the innovative agent to a generic and the exchange of one generic to another. The author also mentions the legal points and criticizies the regulations available in some countries allowing a free exchange of the bioequivalent drugs without the agreement of the physician or the patient. The final part of the paper reviews the results of the comparative studies on the effects of the generic antiepileptic drugs and the experiences of the physicians of their application based on surveys performed with questionnaires. The data of the literature is compared to the Hungarian methods of application and to his own experience. Recommendations for the application of generic antiepileptic drugs are summarized in „twelve points“.]

Clinical Neuroscience

SEPTEMBER 30, 2008

[Antiepileptic drugs as mood stabilizers: what did we learn from the epileptology?]


[Author summarizes the practical aspects of psychiatric application of mood stabilizing antiepileptic drugs. He observes how to transfer experiences taken from the “epileptological” practice into the psychiatric care of bipolar patients. He shortly demonstrates the relevant information on the mechanisms of action, controversies and possible clinical effects influenced by the seizure inhibiting effect of the concerning molecules. By the opinion of the author the clinical importance of pharmacokinetic parameters are underestimated in the psychiatric practice. Therefore - as an original approach in the literature - he summarizes the detailed clinical indications of serum level measurements of antiepileptic drugs applied in psychiatry as mood stabilizers. The therapeutic experiences in epilepsy added a lot of practices for the most effective dosing, building, tapering and exchange of the mood stabilizer antiepileptics. Drug interactions (appear among the psychotropic drugs or with the commonly used medicines). As in any chronic therapies the main condition of patient's compliance is the lacking or very mild presence of the applied therapy. The paper discusses the most frequently occurring and drug-specific side effects in table forms. Using the term of “relative therapeutic potential” the need of balance between the efficacy (influenced by the choice and dosing) and the tolerance are pointed. Rules of application can change significantly in special populations like in pregnancy, obesity, chronic diseases or in chronic comorbide states and in case of polytherapy. As for the special therapeutic effects, the experiences are not completed even in group of antiepileptics: we have larger and more favorable knowledge on the traditional drugs (carbamazepine and valproates) and on lamotrigine (from the newer generation) but promising but not enough information exists on the newest antiepileptic molecules. Further targeted studies are needed for the identification and positioning of antiepileptic drugs in the palette of mood stabilizing pharmacotherapy and for the definition of evidence based, individually tailored and lifelong applied highly effective combinations of the mood stabilizing pharmacotherapy containing antiepileptic agents.]