The aim is to determine how well the parameters of the Weibull model of dissolution can be estimated in dependency on the chosen times to measure the empirical data. The approach is based on the theory of Fisher information. We show that in order to obtain the best estimates the data should be collected at time instants when tablets actively dissolve or at their close proximity. This is in a sharp contrast with commonly used experimental protocols when sampling times are distributed rather uniformly.
Polyamidoamine dendrimers (PAMAMs) of generations 1 (G1) and 4 (G4) were conjugated with a bifunctional pyridine-N-oxide DOTA analog, 10-[(4-carboxy-1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(4)do3a-py(NO-C)), through the pyridine-4-carboxylic acid group, and the conjugates were radiolabeled with indium-111. Reaction conditions for the radiolabelling were optimized. Both radiolabeled conjugates, G1-[(111)In(do3a-py(NO-C))] and G4-[(111)In(do3a-py(NO-C))], were kinetically stable for at least 48h after preparation; in the presence of competitive ligands, the radiochemical purity of the conjugates slightly decreased (4-7%) over the same time period. The preclinical pharmacokinetics of both agents were evaluated. Biodistribution and elimination in rats were more favorable for the G1-[(111)In(do3a-py(NO-C))] conjugate than G4-[(111)In(do3a-py(NO-C))] conjugate. However, the G1-[(111)In(do3a-py(NO-C))] conjugate was rapidly eliminated from the body, mainly through urine, while, significant and long-term radioactivity uptake in the liver and kidney was observed for the G4-[(111)In(do3a-py(NO-C))] conjugate.
- MeSH
- dendrimery chemie farmakokinetika MeSH
- heterocyklické sloučeniny monocyklické chemie farmakokinetika MeSH
- izotopové značení metody MeSH
- krysa rodu rattus MeSH
- nosiče léků chemie farmakokinetika MeSH
- potkani Wistar MeSH
- pyridiny chemie farmakokinetika MeSH
- radiofarmaka chemie farmakokinetika MeSH
- radioizotopy india chemie farmakokinetika MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cardiotoxicity represents the main drawback of clinical usefulness of anthracycline antineoplastic drugs. In this study, a content of selected elements (Ca, Mg, K, Se, Fe) in the post-mortem removed samples of the myocardial tissue was studied in three groups of rabbits: 1) control group (i.v. saline; n = 10); 2) daunorubicin-receiving animals (DAU; 3 mg/kg, i.v; n = 11); 3) animals receiving cardioprotective iron-chelating agent dexrazoxane (DEX; 60 mg/kg, i.p.; n = 5) prior to DAU. Drugs were administered once weekly for 10 weeks. 5-7 days after the last administration, cardiac left ventricular contractility (dP/dtmax) was significantly decreased in DAU-treated animals (745 +/- 69 versus 1245 +/- 86 kPa/s in the control group; P < 0.05), while in the DEX + DAU group it was insignificantly increased (1411 +/- 77 kPa/s). Of the myocardial elements' content studied, a significant increase in total Ca against control (16.2 +/- 2.4 versus 10.6 +/- 0.9 microg/g of dry tissue; P < 0.05) was determined in the DAU-group, which was accompanied with significant decreases in Mg and K. In the heart tissue of DEX-pretreated animals, no significant changes of elements' content were found as compared to controls, while the Ca content was in these animals significantly lower than in the DAU group (9.1 +/- 0.4 versus 16.2 +/- 2.4 microg/g; P < 0.05). Hence, in this study we show that systolic heart failure induced by chronic DAU administration is primarily accompanied by persistent calcium overload of cardiac tissue and the protective action of DEX is associated with the restoration of normal myocardial Ca content.
- MeSH
- antibiotika antitumorózní toxicita MeSH
- antracykliny toxicita MeSH
- draslík metabolismus MeSH
- financování organizované MeSH
- hořčík metabolismus MeSH
- kardiomyopatie chemicky indukované metabolismus MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus MeSH
- razoxan toxicita MeSH
- selen metabolismus MeSH
- stopové prvky metabolismus MeSH
- vápník metabolismus MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
