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W Lasek M Jakóbisiak M Grochowska D Górecki R Gniadecki P Kaliński 《Transplantation》1989,47(5):913-915
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Summary In 73 patients on digitoxin maintenance medication a progressive increase of mean serum digitoxin activity was found with increasing dose. However, there were considerable variations within each group. Change of dose was followed by a new steady state level close to that predicted by zero order absorption-first order elimination kinetics of the drug. In atrial fibrillation the expected fall in ventricular rate was always observed with increasing serum concentration. No significant difference in serum level was found 24 h after identical peroral and intravenous doses had been given to different groups of patients. However, significantly higher serum values were found in normal subjects than in patients with heart disease after identical peroral treatment. This probably indicates poorer absorption by the patients. In 13 subjects, the estimated serum digitoxin half-lives were 3.7 to 11.3 days. These large differences may explain much of the variation in serum values found during steady state therapy. The elimination curves were in accordance with a first order drug kinetics. Only three patients with definite digitalis intoxication were seen, all of whom had high serum values which did not overlap patients without features of intoxication. The results showed that several patients on maintenance therapy were under-digitalized. It is hoped that this or similar methods may make it possible to adjust individual treatment to compensate for differences in absorption, distribution and elimination, and thereby to increase the benefits and decrease the risks of toxicity of digitoxin therapy. 相似文献
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Several new 2-substituted derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one were synthesized. The derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one (1-4) were used as the substrates. These compounds were converted by the reactions of cyanoethylation, hydroxymethylation and aminomethylation into appropriate 2-substituted derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one (5-28). Some of these compounds (5, 9 and 16) show anticonvulsant activity, while compounds 6, 7, 11-13 and 20 possess immunosuppressive activity. 相似文献
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