年龄对地高辛临床药代动力学的影响

本文用Ｂａｙｅｓｉｎ一点法拟合心衰病人的ＤＧ个体药代动力学参数，重点考察年龄对ＤＧ药代动力学的影响。结果显示，老年组的ＣｒＣＬ、ＣＬ和Ｖｄ显著低于中青年组（Ｐ＜０．０５），年龄与ＣｒＣＬ、ＣＬ和Ｖｄ相关显著（Ｐ＜０．０５），ＣｒＣＬ与ＣＬ、Ｖｄ和Ｄ１．０存在良好的正相关（Ｐ＜０．０１）。表明随着年龄的增长，肾功能逐渐下降，ＤＧ的ＣＬ和Ｖｄ逐渐减少，且肾功能下降与ＣＬ和Ｖｄ减少呈平行关系。老年组个体参数变异更大。     

老年因素对地高辛药代动力学的影响

就国内、外常见老年人心力衰竭的常用药物－地高辛的吸收，分布，代谢及给药剂量并加以讨论。     

冠心病心力衰竭不同中医证型对地高辛药代动力学的影响

目的：研究冠心病充血性心力衰竭肾阳虚衰证与心血瘀阻证对地高辛药代动力学的影响。方法：将冠心病充血性心力衰竭患者分为肾阳虚衰与心血瘀阻两组，两组患者均口服地高辛片剂。检测两组地高辛稳态血药浓度，血清肌酐，尿素氮，并用Bayesian一点法拟合地高辛的个体药动学参数，进行统计学比较，结果：肾阳虚衰组稳态血药浓度，血清肌酐 ，尿素氮水平均显著高于心血瘀阻组，且较心血瘀阻组地高辛在体内分布容积明显减少，生物半衰期延长，消除速度减慢，结论：地高辛在不同证型的患者体内的药代动力存在差异，肾功能衰减是造成差异的原因之一。而肾功能的衰退与肾阳虚衰关系密切。     

口服地高辛的药代动力学影响因素的研究进展

地高辛是临床上治疗充血性心力衰竭(congestive heart failure,CHF)的主要药物。由于其安全范围窄,个体差异大,用药干扰因素影响较大,目前在临床应用过程中常对其血清浓度进行检测。患者性别、年龄、特殊病/生理状态以及合用药物等是影响血清地高辛浓度的主要因素。在诸多因素中,合并用药所带来的问题最多。临床应用地高辛时,应关注可影响其血药浓度的各种因素,做到安全合理用药。     

卡托普利对兔体内地高辛药动学的影响

<正>近几年来,血管紧张素转换酶抑制剂(ACEI)卡托普利(Captopril简CPT),常与地高辛合用,治疗充血性心力衰竭,获得了良好效果.有文献报道,CPT与地高辛合用后可显著提高地高辛的血药浓度;另有报道,加服CPT前后,地高辛血药浓度,两者间无显著性差异.为了合理用药,减少药物的毒副作用,本实验在无其他药物干扰的情况下,就CPT对地高辛的药代动力学的影响,用家兔进行研究,为临床更合理地用药,提供依据.     

布美他尼与地高辛相互作用及药代动力学考察

采用紫外光谱法测定布美他尼血药浓度及在家兔体内药代动力学参数，并对13例心衰患者合用地高辛后体内相互作用进行了考察。结果表明，两药合用无明显相互作用影响。     

影响地高辛药动药效特性的药物因素及处理

影响地高辛药动药效特性的药物因素及处理刘晓明（河北张家口医学院第一附属医院０７５０００）地高辛（Ｄｉｇｏｘｉｎ）是临床上治疗心力衰竭的强心甙类药物之一。其药动药效特性受多种因素的干扰。本文就与之有关的药物因素作如下综述，以供医师、药师参考。１心血管用...     

氟嗪酸的药代动力学和临床应用

氟嗪酸(Ofloxacin,OFLX)是一种新的喹啉羧酸类衍生物,生物活性显著。1985年已在联邦德国和日本上市。OFLX主要作用机制是抑制细菌的DNA旋转酶,阻断DNA的合成,从而产生快速杀菌作用。该药抗菌谱广,对包括厌氧菌的革兰氏阳性和阴性细菌均有很强的抗菌活力,对葡萄球菌、溶血链球菌和肠球菌的抗菌活性比氟哌酸强2～4倍,对肺炎链球菌的作用是氟喹诺酮药物中最强的。且对枝原体,衣原体     

MDR1 Genotype-Related Pharmacokinetics of Digoxin After Single Oral Administration in Healthy Japanese Subjects

Purpose. To evaluate the MDR1 genotype frequency in the Japanese population and to study the relationship between the MDR1 genotype and the pharmacokinetics of digoxin after single oral administration in healthy subjects. Methods. The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg. Results. It was found that 35.1 % (40/114) of subjects were homozygous for the wild-type allele (C/C), 52.6 % (60/114) were compound heterozygotes with a mutant T-allele (C3435T) (C/T), and 12.3 % (14/114) were homozygous for the mutant allele (T/T). There was no effect of gender or age on the distribution. The serum concentration of digoxin after a single oral administration increased rapidly, attaining a steady state in all subjects; however, it was lower in the subjects harboring the T-allele. AUC_{0-4 h} values (±SD) were 4.11 ± 0.57, 3.20 ± 0.49, and 3.27± 0.58 ng h/ml, respectively, with a significant difference between C/C and C/T or T/T. Conclusions. The serum concentration of digoxin after single oral administration was lower in the subjects harboring a mutant allele (C3435T) at exon 26 of the MDR1 gene.     

地高辛中毒病人的临床药物动力学变化

本文对81例心衰病人的地高辛（DG）临床药物动力学资料进行研究，探讨中毒病人与非中毒病ADG临床药物动力学的差异及影响因素。结果中毒组病人的DG药物动力学参数与非中毒组病人存在极显著性差异（P＜0．01）、CL减少37．9％，Vd减少8．3％，T1／2延长43．5％，K减少1／3；给药剂量也应较非中毒病人减少40％，才能确保用药安全。中毒组病人年龄显著高于非中毒病人（P＜0．01），提示DG中毒多发生于老年心衰病人。而中毒组病人的肾功能显著低于非中毒病人（P＜0．01）。相关分析显示，年龄与肾功能、心功能、CL和Vd相关极为显著（P＜0．01），肾功能与DG药物动力学参数、心功能存在显著相关。     

1例支气管扩张合并地高辛中毒患者的药学监护

目的探讨临床药师在重症感染伴药物中毒患者治疗方案中的作用与药学监护的切入点。方法临床药师参与1例重症感染伴地高辛中毒患者的治疗,对地高辛及万古霉素进行血药浓度监测,根据血药浓度调整给药剂量,减少了不良反应的发生。结果临床药师的建议被医生采纳,及时调整了地高辛的剂量,纠正了药物中毒。结论临床药师可从自身学科的特点出发,找到临床监护的切入点,协助医生制定安全、有效的治疗方案。     

地高辛在老年慢性心功能不全患者中的应用及其血药浓度变化研究

目的：观察地高辛治疗老年慢性心功能不全的临床疗效,探讨地高辛血药浓度监测的价值。方法：选取2012年10月—2014年6月在广州市番禺区何贤纪念医院应用地高辛治疗的老年慢性心功能不全住院患者146例,观察其临床疗效,并测定地高辛稳态血药浓度。结果：心力衰竭缓解患者地高辛稳态血药浓度为（1．64±0．87）ng／ml,心力衰竭未缓解患者为（0．82±0．41） ng／ml,差异有统计学意义（P＜0．05）;地高辛血药浓度越高,中毒反应发生率越高,差异有统计学意义（P＜0．05）;患者年龄、给药剂量、联合用药等均对地高辛血药浓度存在影响。结论：地高辛血药浓度个体差异较大,血药浓度监测对减少地高辛中毒和实现个体化给药具有重要意义。     

Pharmacokinetics of digoxin in the turkey and comparison with other species

Digoxin was administered by bolus intravenous injection to seven broad-breasted white turkey poults at doses of 0.1, 0.15, or 0.2 mg/kg. Plasma digoxin concentrations were measured by a ¹²⁵ I radioimmunoassay at selected times over the subsequent 24 hr. The data were fitted to a two compartment open pharmacokinetic model. Overall mean values for kinetic variables were: distribution halflife, 38.96 min; elimination halflife, 11.03 hr; volume of distribution in the central compartment, 1.54 liters/kg; total body clearance, 5.81 ml/min/kg. Different doses did not appear to have a significant effect on the identifiable pharmacokinetic variables, suggesting that digoxin disposition is dose independent in the turkey. The results obtained in turkeys were compared with data reported for rats, cats, dogs, and humans. The value for total body clearance of digoxin in the turkey was similar to values found in man, dogs, and cats but considerably less than values reported for rats. The value for elimination halflife in turkeys was somewhat less than values reported for infants and dogs; however, it was considerably different than values reported for rats and cats.This work was supported in part by NIH Grant HL 18204 and the Dwan Family Fund.     

某院门诊2003-2005年地高辛合并用药分析

目的了解地高辛的合并用药情况，为临床合理用药提供参考。方法利用浙江省医院管理系统药房管理子系统，对2003年3月-2005年12月期间某院所有舍地高辛的门诊处方进行回顾性分析。结果与地高辛有药代动力学相互作用的合并用药包括11种口服抗菌药物、13种P-糖蛋白抑制剂和2种促胃肠动力药，分别占地高辛总处方量的5．5％，64．7％和0．7％。同一张处方中与地高辛并用药物含2种以上P-糖蛋白抑制剂的占5．2％，含口服抗菌药物与P-糖蛋白抑制剂的占3、2％。结论地高辛在目前临床合并用药中，产生药代动力学相互作用的可能性较大。药师应做好处方审查和患者用药教育；在加用或撤除一些并用药物时，必须注意可能引起的地高辛药代动力学变化；必要时对某些可疑相互作用进行血药浓度监测。     

Inotropic Effect of Digoxin in Humans: Mechanistic Pharmacokinetic/Pharmacodynamic Model Based on Slow Receptor Binding

Purpose. The purpose of this study was to construct a mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for digoxin that describes the relationship between plasma concentration and inotropic response. Methods. On the basis of results obtained in the isolated perfused rat heart, a PK/PD model for digoxin in humans was developed. In fitting the model to previously published bolus dose and concentration clamp data (shortening of electromechanical systole), the plasma concentration-time curves were used as forcing functions in the computer program ADAPT II. Results. The mechanistic approach allowed a modeling of digoxin pharmacodynamics which is consistent with available inotropic response data. The estimates of the receptor binding parameters were in the same order of magnitude as those measured in vitro for ouabain. The mechanistic model explained the parameters of the empirical link model (EC₅₀, E _max and delay time ) in terms of the underlying processes, suggesting that the long equilibration half-time of 13 h is due to slow receptor binding. The empirical link model, in contrast, is not compatible with a noninstantaneous receptor binding process and led to estimates of the delay time that were dependent on the digoxin administration schedule. Conclusions. The new, mechanistic model may provide a rationale for better understanding of digoxin pharmacodynamics and could become a tool to bridge the gap between in vitro and in vivo studies.     

Relationship Between Loperamide-Induced Sedative Effect and Digoxin Pharmacokinetics in Healthy Japanese Subjects

No HeadingPurpose. Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or decline in the P-glycoprotein (P-gp) function. The aim of this study was to determine the loperamide-induced sedative effect quantitatively and to investigate possible alterations in the pharmacokinetics of digoxin, a substrate for P-gp, in Japanese subjects.Methods. Loperamide hydrochloride (2 mg) was administered orally to 26 subjects and the critical flicker-fusion frequency threshold (CFF) values were measured every 30 min separately by portable instrument. Further, digoxin (0.25 mg) was administered to 8 subjects, and the plasma concentration was determined.Results. In five subjects who complained of drowsiness, the CFF values more remarkably decreased compared with those in the other subjects. The T_max and mean residence time (MRT) values of digoxin pharmacokinetics in four subjects with drowsiness were significantly lower and C_max was higher than those in four subjects with marginal effect. Moreover, there were good correlations between the CFF value-time profile and the C_max, T_max, and MRT of digoxin.Conclusions. The determination of the CFF value after oral administration of loperamide will be useful for evaluating varied P-gp function and for anticipating individual variations in the disposition of P-gp substrates in humans.     

Digoxin infusion versus bolus injection in rapid atrial fibrillation: relation between serum level and response

Summary Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart.In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8–9 h in the infusion group and after 19–20 h in the bolus injection group, without any detectable difference in side effects.There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients.However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.     

辛伐他汀在治疗舒张性心力衰竭中的疗效观察

目的探讨辛伐他汀治疗舒张性心力衰竭的临床效果。方法选择65例舒张性心力衰竭患者,随机分为观察组和对照组。两组患者均给予常规治疗,观察组患者同时给予辛伐他汀。观察两组患者治疗前和治疗后的心功能分级、6 min步行距离、超声心动图改变情况。结果观察组治疗后的心功能分级、6 min步行距离分别和对照组治疗后比较,差异有统计学意义(P<0.05);观察组治疗后的E峰、E/A、左心室等容舒张时间分别和对照组治疗后比较,差异有统计学意义(P<0.05)。结论辛伐他汀能够显著改善舒张性心力衰竭患者心功能,疗效显著。