1,720,984 research outputs found
Pharmacogenetics: Pharmacokinetics and clinical implications [Farmacogenetica: Farmacocinetica ed implicazioni cliniche]
No full textIn the last years, pharmacogenetic studies tried to identify the hereditary bases characterizing different individual response to drugs. Human organism tries to remove drugs by activating enzyme systems. Metabolization reaction rate shows wide interindividual variations, being characterized by different factors, such as physiologic (age, sex), pathologic (liver and kidney diseases), and genetic characteristics. Inborn errors may lead to some alterations in functional enzyme activities. These alterations led to divide the whole population into two groups: slow metabolizers PM (having a slow metabolism), and fast metabolizers EM (having a normal metabolism). Such a different behaviour may lead to changes in pharmacokinetic parameters which may also influence pharmacodynamic characteristics of the drug, thus leading to: 1) an excessive therapeutic effect, 2) a decreased therapeutic effect, 3) an increased toxicity of the drug not undergoing its transformation, 4) toxicity of a metabolic byproduct formed by a pathway different from the main one
A short introduction to pharmacokinetics
No full textPhamacokinetics is proposed to study the absorption, the distribution, the biotransformations and the elimination of drugs in man and animals. A single kinetic profile may be well summarized by Cmax, Tmax, t1/2 and AUC and, having more than one profile, 8 parameters at least, the mean and standard deviation of these parameters, may well summarize the drug kinetics in the whole population. A more carefull description of the data can be obtained interpolating and extrapolating the drug concentrations with some mathematical functions. These functions may be used to reduce all the data in a small set of parameters, or to verify if the hypotheses incorporated in the functions are confirmed by the observations. In the first case, we can say that the task is to get a simulation of the data, in the second to get a model. The functions used to interpolate and reduce the pharmacokinetic data are the multiexponential functions and the reference models are the compartmental models whose solutions are just the multiexponential functions. Using models, new meaningfull pharmacokinetic parameters may be defined which can be used to find relationships between the drug kinetic profile and the physiological process which drive the drug absorption, distribution and elimination. For example, compartmental models allow to define easily the clearance which is dependent on the drug elimination process, or the volume of distribution which depends on the drug distribution in the tissues. Models provide also an easy way to get an estimate of drug absorption after extravasculare drug administration (bioavailability). Model building is a complex multistep process where, experiment by experiment and simulation by simulation, new hypothesis are proven and disproven through a continuous interaction between the experimenter and the computer
Variations of peripheral markers of serotoninergic system in selected vascular patients
No full textBACKGROUND AND AIM: Serotonin (5-HT), a decarboxylated derivative of tryptophan, is synthesized in the enterochromaffin cells and released into blood stream to be incorporated into platelets. At the site of endothelial lesions, platelets aggregate and secrete 5-HT that presents several vascular actions involved in thrombosis and atherogenesis. In fact, 5-HT may induce vasoconstriction in the presence of endothelial injury, aggregation of platelets, and mitogenesis of arterial smooth muscle cells and endothelial cells. It may also contribute to the vascular inflammation associated with atherogenesis by increasing the synthesis of Interleukin-6 in vascular smooth muscle cells. We evaluated serotonin levels in plasma and platelets of patients with unstable angina and ischemic stroke, to identify an association between serotonin and atherosclerosis of coronary and cerebral arteries.
METHODS AND RESULTS: Twenty patients (14 men, 6 women, mean age 69 +/- 10 years) with unstable angina and 15 patients (7 men, 8 women, mean age 81 +/- 10 years) with ischemic stroke were included in the study. Twenty-four healthy subjects matched for age and sex constituted the control group. Blood samples were drawn in the morning to determine plasma and platelet concentrations of serotonin. In patients with unstable angina serotonin levels in platelets were significantly lower (p < 0.001) than those observed in controls, while serotonin concentrations in plasma did not significantly differ from those found in controls. In patients affected by stroke serotonin levels in plasma and in platelets did not significantly differ from those found in normal subjects.
CONCLUSIONS: Our findings may contribute to the knowledge to different mechanisms involved in the pathogenesis of cardiac and cerebral ischemia
Stimulation of endogenous adenosine release by oral administration of quercetin and resveratrol in man
No full textEpidemiological evidence indicates that moderate alcohol consumption is associated with a significant decrease in the incidence of certain cardiovascular disorders, which can lead to impaired quality of life and to death. However, there are no objective data suggesting a cause-effect relationship and detailed research based on definitive working hypotheses is needed. We tested two flavonoids in man and found that these substances can belong, at least in part, to a wine-dependent mechanism, which leads to increased adenosine plasma levels. If these results could be confirmed by analyzing all the possible influences leading to blood nucleoside increase, a hypothesis of diet-dependent cellular preconditioning could be discussed
Role of basal inflammatory status as a predictor of survival in bevacizumab-treated advanced non-small cell lung cancer (NSCLC) patients
No full textEffect of two single oral doses of mesoglycan on the coagulative and fibrinolytic system in human. A pharmacodynamic study [Azione di due dosi orali singole di mesoglicano sul sistema coagulativo-fibrinolitico dell'uomo. Studio farmacodinamico]
No full textIn this study the profibrinolytic activity of two single oral doses of mesoglycan was evaluated. Furthermore, a mathematical model describing the patterns of the resulting phenomena was applied. Ten patients with impaired fibrinolytic system (euglobulin lysis time > 180 min) were enrolled in the study. In the morning following a 24 hour fast period, the patients were given orally a single dose (100 and 50 mg) of mesoglycan and placebo, with an interval of 48 hours between each treatment. The following parameters were evaluated at the time 0 and after 2, 4, 6, 8, 10 and 12 hours from each administration: tissue plasminogen activator (t-PA) and its inhibitor PAI-1, euglobulin lysis time, plasminogen and alfa-2-antiplasmin as indexes of the fibrinolytic system; aPTT, TT, fibrinogen as indexes of the hemostatic-coagulative system. Mesoglycan showed a dose-dependent profibrinolytic activity, that was also present after placebo but in a less entity. The mathematical study confirms the experimental observations and thus may allow to describe, with a high degree of approximation, the in vivo pharmacology of mesoglycan through the use of the mathematical function
Cardiac dysautonomia and serotonin plasma levels in Rett syndrome
No full textBACKGROUND:
In Rett syndrome the autonomic nervous system is abnormal at various levels, from the central to the peripheral nervous system. A role for serotoninergic dysfunction has been suggested.
OBJECTIVES:
The aim of our study was to evaluate the relation between cardiac dysautonomia (expressed by means of heart rate variability) and plasma serotonin levels in girls affected with Rett syndrome. Heart rate variability and plasma serotonin levels were evaluated in 28 Rett girls aged 1-14 years. A Pearson correlation was used to determine whether there was a relationship between plasma serotonin levels and each heart rate variability parameter.
RESULTS:
In untreated Rett girls the plasma serotonin levels correlated with the sympathovagal balance, as expressed by the low frequency (LF) to high frequency (HF) ratio (p<0.05).
CONCLUSIONS:
Our results suggest that cardiac dysautonomia could be linked to serotoninergic dysfunction and that treatment with a serotonin analogue could be useful in improving the sympathovagal balance
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