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Aim To study the absorption kinetics of se-ries molecular weight 5-ASA-mPEG in rats intestine. Methods The in situ intestinal absorption property of 5-ASA-mPEG in rats was investigated by means of sin-gle-pass perfusion, and HPLC method was established to determine the drug concentration in the perfusate. Results The drug concentration and the site of intes-tine segments had little effect on the drug absorption constant ( Ka ) and apparent absorption coefficient (Papp). The perfusion flow rate and the variable mo-lecular weight of 5-ASA-mPEG could significantly af-fect the Ka and Papp. Conclusion 5-ASA-mPEG can be absorbed at all segments of the intestine of rats and has no specific absorption site. It is preliminarily in-ferred that the absorption mechanism of 5-ASA-mPEG is passive transportation. The intestinal absorption of 5-ASA-mPEG shows a downward trend with the increase in molecular weight. The results shows that the modifi-cation of 5-ASA by PEG can effectively inhibit the in-testinal absorption of mesalazine.
RESUMO
Objective To assess the diagnostic value of chronotropic index in identifying coronary artery disease (CAD). Methods One hundred and sixty two patients with suspected CAD were referred for a routine treadmill exercise electrocardiogram and subsequently underwent selective coronary angiography within 3 weeks. The magnitude of ST segment depression and chronotropic index were measured by a computerized ECG system. CAD was defined by coronary angiography. Results In detecting CAD, the sensitivity was 70. 1% versus 60.9% (P< 0.05) ,the specificity was 84.0% versus 73.3% (P<0.05), and the accuracy was 76.5% versus 66.7% (P< 0.05) by chronotropic index and standard electrocardiographic test criteria. The value of Kappa statistic for chrono-tropic index consistency in our experiment was 0.534(>0.4). The number of diseased vessels was correlated with the mean value of chronotropic index. The chronotropic index decreased from 0.88±0.09 in patients without coro-nary disease to 0.68±0.06 in those with 3 vessels involved (P<0.01). A more closed relationship was found be-tween chronotropic index and lesion in the fight coronary artery. Conclusions Chronotropic index is possibly a valu-able positive index for the diagnosis of CAD. The sensitivity,specificity and accuracy of chronotropic index are signif-icandy higher than those of standard electrocardiographic test criteria in identifying CAD.
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In this report, highly water soluble esters of scutellarin with different molecular weight polyethylene glycol (PEG) were synthesized in order to improve the bioavailability of scutellarin. The physicochemical properties, the stabilities under different conditions and the in situ intestinal absorption in rats of the conjugates were investigated. By PEG modification, the greatly increased water solubility and desirable partition coefficient of scutellarin were obtained. These compounds function as prodrugs i. e. breakdown occurred in a predictable fashion: the t1/2 of them in PBS buffer at pH7.4 was above 12 h (37 degrees C) in vitro, while in plasma a rapid breakdown was observed, with a t1/2 of about 1. 5-3 h. The stabilities of the prodrugs were improved according to the increase of the molecular weight of PEG, thus, PEGylated prodrugs with desirable rates of hydrolysis could be obtained by the use of variable molecular weight PEGs. The PEGylation could enhance the absorption of scutellarin in rat intestine, and the absorption of scutellarin and its PEG conjugates by intestine was mainly via passive transport, for when the concentration was raised, the uptake did not appear saturable, and the permeability coefficient kept at an equilibrium level. When the molecular weight of PEG increased from 200 to 1000 Da, the absorption of the conjugates decreased. In conclusion, by overall consideration of the yield, stability and absorption, the present authors estimate that the PEG molecular weight used for the PEGylation of scutellarin should be within the range of 400-1 000 Da.