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重症监护患者以及接受麻醉和手术患者的地高辛血浆浓度(作者译)

[Plasma concentrations of digoxin in patients under intensive care conditions and in patients undergoing anesthesia and operation (author' transl)].

作者信息

Rietbrock I, Streng H, Pesold R

出版信息

Klin Wochenschr. 1978 May 15;56(10):503-17. doi: 10.1007/BF01492863.

Abstract

Pharmacokinetic behavior of digoxin or beta-acetyldigoxin was examined in 66 patients (27 patiets under intensive care conditions, partially with controlled breathing, 22 patients undergoing extirpation of the uterus and 17 patients treated with radium or chemotherapeutics; 19 males and 47 females) by determining plasma concentrations of digoxin (PDC). After intravenous and oral application with a maintenance dose of 0.20--0.50 mg/day blood was taken daily during a 2 to 3 week period, resulting in 510 determinations. 24 hours after the first application of 0.50 mg digoxin i.v. the mean values of PDC amounted to 0.62 +/- 0.08 ng/ml. After 0.40 or 0.25 mg digoxin per day i.v. therapeutical concentrations could be observed at the third vs fifth day. An equilibrium of PDC was reached on the 6th day after starting digitalization using maintenance doses. Intravenous application of 0.25, 0.40 or 0.50 mg digoxin per day resulted in a mean steady state of 0.68 +/- 0.37, 0.86 +/- 0.33 or 1.27 +/- 0.49 ng/ml PDC, respectively. The results were significantly different (p less than 0.01--0.001). Serial measurements indicated a great variation of PDC. In patients without renal failure the intraindividual variation of the plasma concentrations was maximal 37.4% referring to the mean steady state, interindividual 37.1% and the evaluation of the inter- and intraindividual differences amounted to 54.1%. After oral administration of digoxin (maintenance dose: 0.50 mg/day) or beta-acetyldigoxin (maintenance doses: 0.20--0.40 mg/day) differences in PDC of 38.3% and 29.7% were obtained. Body weight, age and serum creatinine concentration were partly responsible for the variance of PDC. Multiple linear regression between stead state PDC and dose, age, body weight and serum creatinine concentration revealed 62.1% of the variance of the PDC after intravenous administration of digoxin. After oral administration of beta-acetyldigoxin 39.9% were obtained. Thus, 40% of the variance were caused by differences in distribution and elimination of digoxin after i.v. application. After oral application additional 20% of the variance could be attributed to resorption and possible disturbances.

摘要

通过测定地高辛的血浆浓度(PDC),对66例患者(27例在重症监护条件下,部分患者呼吸受控;22例接受子宫切除手术;17例接受镭疗或化疗;男性19例,女性47例)的地高辛或β-乙酰地高辛的药代动力学行为进行了研究。静脉注射和口服维持剂量为0.20 - 0.50mg/天后,在2至3周内每天采血,共进行了510次测定。静脉注射0.50mg地高辛后24小时,PDC的平均值为0.62±0.08ng/ml。静脉注射每天0.40或0.25mg地高辛后,在第三天和第五天可观察到治疗浓度。使用维持剂量开始洋地黄化后第6天达到PDC平衡。静脉注射每天0.25、0.40或0.50mg地高辛,分别导致PDC的平均稳态为0.68±0.37、0.86±0.33或1.27±0.49ng/ml。结果有显著差异(p<0.01 - 0.001)。系列测量表明PDC有很大差异。在无肾衰竭的患者中,血浆浓度的个体内差异相对于平均稳态最大为37.4%,个体间差异为37.1%,个体间和个体内差异的评估为54.1%。口服地高辛(维持剂量:0.50mg/天)或β-乙酰地高辛(维持剂量:0.20 - 0.40mg/天)后,PDC差异分别为38.3%和29.7%。体重、年龄和血清肌酐浓度部分导致了PDC的差异。稳态PDC与剂量、年龄、体重和血清肌酐浓度之间的多元线性回归显示,静脉注射地高辛后,PDC差异的62.1%可由此解释。口服β-乙酰地高辛后为39.9%。因此,40%的差异是由静脉注射后地高辛分布和消除的差异引起的。口服后,另外20%的差异可归因于吸收和可能的干扰。

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