地高辛的体内分析方法应用与进展

目的总结地高辛血药质量浓度监测方法,寻求最适的测定方法。方法对近年来国内外与地高辛监测相关的文献进行检索综述分析。结果地高辛血药浓度测定方法很多,常用方法主要有:FPIA、酶免疫分析法、RIA、CLIA、乳胶免疫抑制法、干化学法、HPLC法等。结论通过比较分析其中RIA、CLIA、EIA和HPLC MS 4种方法更好。     

血肌酐值法预测地高辛个体化给药方案

在地高辛常规监测中，用血肌酐值法预测个体化药动学参数和给药方案。结果表明，８４例病人的地高辛药物动力学参数预测值为，ＣＬ７６±２１ｍｌ／（ｋｇ·ｈ），Ｖｄ７．０５±１．２０Ｌ／ｋｇ，Ｔ１／２６６±７ｈ。预测的个体化剂量为３．１±０．９μｇ／（ｋｇ·ｄ），预测的稳态血药浓度（Ｃ＿（ｓｓ））为１．２４±０．３８μｇ／Ｌ，与实测Ｃ＿（ｓｓ）１．２±０．４μｇ／Ｌ比较，差异无显著性（Ｐ＞０．０５）。     

地高辛临床药物动力学参数的预测及个体化给药方案

用Bayesian一点法拟合心衰病人的DG个体药物动力学参数及个体化给药方案,用minitab对软件DG群体药物动力学数据进行统计学分析.以CrCL为固定效应变量,建立系列回归模型,预测心衰病人的DG个体药物动力学参数、个体化给药方案及其对映的(?)ss.结果显示CrCL与DG群体药物动力学参数存在高度的相关(P<0.001),相关系数分别为:CL=0.805,Vd=0.985,T_(1/2)=-0.517,K=0.525,D_(1.0)=0.714.并建立定量回归模型,预测DG个体药物动力学参数,预测参数与实测参数没有统计学差异,其中以Vd预测精度最好,有95%的预测值在实测值的95%置信限以内.与实测值相关系数为0.974,估计标准误差小于3.3%;其次是CL,有2/3的预测值在实测值95%置信限以内,与实测值相关系数为0.797,估计标准误差小于20%;T_(1/2)和K预测结果稍差.CrCL预测的个体化给药方案80%符合最佳个体化给药方案,且两者所对应的(?)ss没有显著性差异.     

Plant cardiac glycosides and digoxin Fab antibody

The potential application of the Digoxin Fab antibody (Wellcome Digibind) in the clinical management of plant poisoning was investigated. The cardiac glycoside contents of various Australian plants were studied using immunoassay techniques. The cross-reactions of the Fab antibody and two digoxin assay antibodies against extracts of these plants were also studied. Results obtained indicated that the Digibind antibody cross-reacted with a wide range of glycosides contained in Australian plants and therefore could be of use in the treatment of life-threatening plant poisoning.     

儿童地高辛血药浓度的回顾性分析

目的 :探讨血药浓度监测对个体化、合理化用药的重要作用。方法 :荧光偏振免疫法 (FPIA)和通过近十年住院病人地高辛用药的回顾性分析。结果 :地高辛血药浓度监测结果分三个范围 :低值小于 0 .8μg/ L,中值 0 .8～ 2 .2 μg/ L,高值大于 2 .2μg/ L。对实验数据进行统计 ,得出有效浓度范围内的病人占 4 0 %左右 ,低值平均约 >5 0 % ,高值平均为 6 .1%。结论 :通过对地高辛用药的监测回顾 ,说明地高辛的药物代谢过程受许多因素如吸收、分布、代谢、排泄、药物间的相互作用等的影响。所以临床在用药过程中 ,药物浓度的监测对实施个体化、合理化用药 ,减少药物中毒的发生起着重要作用     

Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables

Summary Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age >60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD.The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI > the median value, were characterized by a lower daily dose and dosage frequency.Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug.     

内洋地黄素拮抗剂上调缺血再灌注损伤大鼠心肌细胞膜钠泵亚基的表达

目的： 观察内洋地黄素特异性拮抗剂地高辛抗血清对心肌缺血再灌注（MIR）损伤大鼠心肌组织内洋地黄素水平、钠泵活性、线粒体总钙浓度以及钠泵各亚基基因表达的影响，探讨内洋地黄素在心肌缺血再灌注损伤中的作用及其机制。方法: 将56只雄性SD大鼠随机分成7组，每组8只。假手术对照组（sham）：丝线穿过左冠状动脉前降支，但不结扎；缺血再灌注组（MIR）：结扎左冠状动脉前降支30 min，再灌注45 min；生理盐水组（NS）、维拉帕米组（Ver）、小剂量、中剂量、大剂量地高辛抗血清组（ADA）：于再灌注前5 min经股静脉分别注射生理盐水、维拉帕米5 mg·kg^-1、地高辛抗血清8.6 mg·kg^-1、 17.3 mg·kg^-1、34.5 mg·kg^-1，容积均为5 mL·kg^-1，5 min内注射完毕，其余同MIR模型组。再灌注结束后，立即取缺血区左室心肌检测心肌匀浆内洋地黄素水平、心肌细胞膜Na+ K+_ATP酶和Ca2+_Mg2+_ATP酶活性、线粒体总钙浓度；分别采用RT-PCR及Western blotting方法和免疫组化方法检测心肌钠泵α₁、α₂、α₃和β₁亚基mRNA及蛋白水平基因表达的改变。结果: 心肌缺血再灌注损伤时，心肌组织内洋地黄素水平明显升高，心肌细胞膜钠泵和Ca2+_Mg2+_ATP酶活性显著下降，线粒体总钙浓度升高，钠泵α₁、α₂、α₃和β₁亚基在mRNA及蛋白水平基因表达均明显下降；维拉帕米除具有降低线粒体总钙浓度外，对其它各项指标无明显影响。地高辛抗血清呈剂量依赖性地显著降低心肌组织内洋地黄素水平，恢复细胞膜钠泵和Ca2+_Mg2+_ATP酶活性，降低线粒体总钙浓度，上调钠泵α₁、α₂、α₃和β₁亚基mRNA及蛋白水平的基因表达。结论: 心肌缺血再灌注促进机体内洋地黄素分泌增加，后者通过下调心肌细胞膜上的钠泵α₁、α₂、α₃和β₁亚基基因表达抑制钠泵活性，进而抑制Ca2+_Mg2+_ATP酶活性，导致线粒体内钙超载，介导心肌缺血再灌注损伤。内洋地黄素特异性拮抗剂地高辛抗血清通过阻断内洋地黄素的生物学作用，上调钠泵各亚基的基因表达，发挥其抗心肌缺血再灌注损伤的作用。     

Serum digoxin concentration and half-life in newborns

Summary Serum digoxin concentration and half-life were radioimmunologically determined in 9 mature newborns after 7 days medication with digoxin. The newborns were in respiratory distress treated with continuous positive airway pressure or were suspected to have serious congenital heart disease. Loading dose was 26 µg/kg body weight intravenously and 35 µg/kg body weight orally, respectively. Maintenance dose corresponded to 1/8^th of the digitalization dose twice daily.The serum digoxin level 12 h after the last dose varied between 1.4 and 2.5 ng/ml (mean 2.0 ng/ml, Sx=0.4). The serum half-life of digoxin varied between 21.7 and 42.4 h (mean 30.0 h, Sx=7.7). The mean serum half-life of digoxin of 30 h attained values found in adults without renal disease. This suggests that the serum digoxin levels of newborns which are usually higher if compared with those of adults result from higher digoxin doses per unit body weight and not from diminished digoxin elimination.     

On the interaction between phenytoin and digoxin

Summary An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC_0–48 from 31.6 to 24.4 ng · ml^–1 · h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml · min^–1. Assuming no change in -acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml · min^–1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.     

Serum digoxin concentrations in a representative digoxin — Consuming adult population

Summary As part of health examination of a representative sample of an adult population (n=8000) serum digoxin concentration was measured in 661 patients on continuous digoxin therapy. The prescribed mean daily dose of digoxin was significantly higher in men (223 µg) than in women (201 µg); the dose significantly decreased with increasing age. The mean serum digoxin concentration was the same in men and women and it differed insignificantly between age groups, although older persons tended to have a higher concentration. The age — adjusted mean steady state digoxin concentration was 1.02 ng/ml in men and 0.98 ng/ml in women; in about 60% the concentration was within the therapeutic range (0.80–2.00 ng/ml). The concentrations were clearly related to daily dose of digoxin. At equal dose levels old persons tended to have higher concentrations than younger persons. The interindividual variation in serum digoxin concentrations was very wide. However, when digoxin measurements in the same subjects were repeated about three months later, a good correlation between the two measurements was found. The interval between the last dose of digoxin and the collection of blood (up to 41 h) had relatively little effect on individual serum digoxin concentrations. Patients on concomitant thiazide or loop diuretic therapy had the same mean serum digoxin concentration as those not-receiving a diuretic. The mean concentration was significantly higher in patients taking a thiazide or loop diuretic combined with triamterene. The difference may have been due to an interaction between triamterene and digoxin.