This study evaluated the effect of age and renal impairment on pharmacokinetics of trimetazidine (TMZ) in healthy elderly and renally impaired subjects and assess safety and tolerability. In this open-label, multi-dose study, 73 subjects were divided into six treatment groups: (1) 55-65 years; (2) 66-75 years; (3) >75 years (dosing for groups 1-3 [healthy]: B.D. for 4 days), (4) mild renally impaired (dosed B.D. for 8 days); (5) moderate renally impaired (dosed O.D. for 8 days); and (6) severe renally impaired-no dialysis (dosed once every 48 h for 8 days). Blood and urine samples were collected and analyzed. The geometric least squares mean ratios for; Group 2 and 1 of AUC(0-τ)ss was 112.2 (90% CI; 92.0-136.8) and Cmax,ss was 109.9 (89.6-134.8), Group 3 and 1 of AUC(0-τ),ss was 140.5 (115.9-170.3) and Cmax,ss was 137.8 (112.9-168.2), Group 4 and 1 of AUC(0-τ),ss was 114.2 (90.3-144.4) and Cmax,ss was 120.8 (92.5-157.8), Group 5 and 1 of; AUC(0-τ),ss was 213.0 (153.1-296.3) and Cmax,ss was 123.3 (92.2-164.7) and Group 6 and 1 of AUC(0-τ),ss was 247.4 (197.8-309.6) and Cmax,ss was 95.6 (73.0-125.1). Significant increase in systemic exposure of TMZ was observed in subjects; over 75 year's age and renally impaired compared to healthy subjects. TMZ was safe and well-tolerated.

• Klíčová slova
• age, pharmacokinetics, renal-impairment, safety, tolerability, trimetazidine,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• renální insuficience krev   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trimetazidin škodlivé účinky   krev   farmakokinetika   MeSH
• vazodilatancia škodlivé účinky   krev   farmakokinetika   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• trimetazidin MeSH
• vazodilatancia MeSH

Coumarins are a large group of substances, primarily of plant origin. Like their more intensively examined congeners flavonoids, many of them are antioxidants. Although such properties may be advantageous in cardiovascular diseases, it has been shown that coumarins exhibit direct effects on the cardiovascular system which are not based on antioxidant activity. The most common example is the well-known drug warfarin, a synthetic compound derived from natural dicoumarol. Moreover, other coumarins have been shown to possess antiplatelet and vasodilatory potential. Interestingly, the former effect may be mediated by the inhibition of various pathways leading to platelet aggregation, their differing effects on those pathways being due to structural differences between the various coumarins. Conversely, their vasodilatory potential is linked in the majority of cases to the inhibition of increases in intracellular calcium concentration in vascular smooth muscle cells, and in several coumarins also to NO-mediated vasodilatation. Available data on both activities are summarized in this review. At the end of this review, relevant data are provided from a few studies testing the in vivo effects of coumarins on major cardiovascular diseases; the clinical use of warfarin and other coumarin anticoagulants, as well as the limited data on the clinical use of coumarins in chronic venous insufficiency and the possible toxicological effects of coumarins.

• MeSH
• antioxidancia farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• inhibitory agregace trombocytů farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• kardiovaskulární nemoci krev   farmakoterapie   metabolismus   patofyziologie   MeSH
• klinické zkoušky jako téma MeSH
• kumariny farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• lidé MeSH
• molekulární struktura MeSH
• objevování léků MeSH
• vazodilatancia farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• inhibitory agregace trombocytů MeSH
• kumariny MeSH
• vazodilatancia MeSH

A method for the determination of isosorbide-5-mononitrate (5-ISMN) in human plasma by capillary gas chromatography with electron-capture detection was developed and applied to clinical samples. 9-Fluorenone was used as an internal standard, ethyl acetate was employed for liquid-liquid extraction. The advantage of the extraction procedure is the possibility of a direct injection of the plasma extract, without solvent removal/reconstitution of the sample. The precision and accuracy of the method were satisfactory in the concentration range 10-1600 ng/ml. The lower limit of quantification was 10 ng/ml.

• MeSH
• chromatografie plynová MeSH
• dimethylpolysiloxany MeSH
• fluoreny MeSH
• indikátory a reagencie MeSH
• isosorbiddinitrát analogy a deriváty   krev   farmakokinetika   MeSH
• lidé MeSH
• referenční standardy MeSH
• reprodukovatelnost výsledků MeSH
• řízení kvality MeSH
• roztoky MeSH
• silikony MeSH
• vazodilatancia krev   farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• 9-fluorenone MeSH Prohlížeč
• baysilon MeSH Prohlížeč
• dimethylpolysiloxany MeSH
• fluoreny MeSH
• indikátory a reagencie MeSH
• isosorbiddinitrát MeSH
• isosorbide-5-mononitrate MeSH Prohlížeč
• roztoky MeSH
• silikony MeSH
• vazodilatancia MeSH

Novel transdermal permeation enhancers related to stratum corneum ceramides were investigated. The synthesis of a series of simple compounds based on two selected amino acids, L-serine and glycine, and their enhancement activities are reported. Glycine derivative 3 enhanced the permeation of theophylline through human skin in vitro 12.5+/-0.5 times. The relationships between properties of the polar head of the compounds and their activity are discussed.

• MeSH
• aplikace kožní MeSH
• azepiny farmakologie   MeSH
• ceramidy chemická syntéza   farmakologie   MeSH
• difuzní komory kultivační MeSH
• glycin chemie   MeSH
• indikátory a reagencie MeSH
• kožní absorpce účinky léků   MeSH
• lidé MeSH
• pomocné látky MeSH
• serin chemie   MeSH
• techniky in vitro MeSH
• theofylin aplikace a dávkování   farmakokinetika   MeSH
• vazodilatancia aplikace a dávkování   farmakokinetika   MeSH
• vodíková vazba MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azepiny MeSH
• ceramidy MeSH
• glycin MeSH
• indikátory a reagencie MeSH
• laurocapram MeSH Prohlížeč
• pomocné látky MeSH
• serin MeSH
• theofylin MeSH
• vazodilatancia MeSH

We prepared a series of five esters of 6-dimethylaminohexanoic acid, and characterised the compounds by their NMR and IR spectra. Their ability to function as transdermal penetration enhancers was subsequently evaluated using excised human skin as a membrane, modified Franz diffusion cells, and theophylline as a model permeant. The penetration-enhancing efficiency of esters 1-5 was studied in the donor media of propylene glycol and isopropyl myristate, and expressed as the corresponding enhancement factors (EF). All the esters increased the penetration of theophylline through the skin. The enhancement factor for the most active substance, undecyl 6-dimethylaminohexanoate, was 118.5 (+/- 19) from propylene glycol.

• MeSH
• aminokapronáty * MeSH
• kožní absorpce účinky léků   MeSH
• kyselina 6-aminokapronová chemie   farmakologie   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• pomocné látky chemie   MeSH
• spektrofotometrie infračervená MeSH
• techniky in vitro MeSH
• theofylin farmakokinetika   MeSH
• vazodilatancia farmakokinetika   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokapronáty * MeSH
• kyselina 6-aminokapronová MeSH
• pomocné látky MeSH
• theofylin MeSH
• vazodilatancia MeSH

Current evidence strongly suggests that coronary atherosclerosis is a common denominator in patients with stable effort angina pectoris. The concept of pathophysiology of coronary atherosclerosis is presented--angiographic and pathologic evidence now suggest presence of eccentric and irregular atherosclerotic lesions (sometimes associated with plaque rupture) and simultaneously present endothelial dysfunction increases sensitivity of vascular smooth muscles to physical and biochemical stimuli with propensity to spasm. Ischemia is due to an increased myocardial oxygen demand (increased heart rate or blood pressure) that cannot be met because of fixed coronary reserve. The organic nitrates are important drugs for the treatment of patients wit angina. The mechanism(s) of their action is presented--biotransformation and liberation of nitric oxide which stimulates guanylyl cyclase and conversion of GTP (by guanylyl cyclase) to cGMP, which causes vasodilatation but reduces platelet adhesion and aggregation too. Sublingual nitroglycerin and isosorbide dinitrate are effective in the treatment of acute episodes of angina. Long-acting nitrate preparations are effectiveness include intermittent transdermal nitroglycerin, standard formulation and sustained-release isosorbid dinitrate (but better isosorbid-5-mononitrate because of longer duration of action of action and no 1st pass hepatic metabolism) (nitrate-free interval should be of 8-10 hours duration). The place of the therapy with betablockers and calcium channel blockers in angina pectoris is presented as well and their combination with nitrates.

• MeSH
• angina pectoris farmakoterapie   MeSH
• isosorbiddinitrát farmakokinetika   terapeutické užití   MeSH
• lidé MeSH
• nitroglycerin farmakokinetika   terapeutické užití   MeSH
• vazodilatancia farmakokinetika   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• isosorbiddinitrát MeSH
• nitroglycerin MeSH
• vazodilatancia MeSH