1180例次地高辛血药浓度测定结果的分析

目的对2000年1月至2011年12月期间地高辛血药浓度监测情况进行分析,旨在为临床合理用药提供药学服务.方法采用荧光免疫偏振法(FPIA)监测地高辛血药浓度,对1180例次血药浓度监测结果进行比较分析.结果地高辛安全有效血药浓度范围是0.5~2.0ng/ml,1180例次地高辛血药浓度测定值在安全有效浓度范围699例次(占59.2%),低于血药浓度范围下限(<0.5ng/ml)336例次(占28.5%),高于血药浓度范围上限(>2.0ng/ml)145例次(占12.3%).结论影响地高辛血药浓度及疗效的因素诸多,临床使用地高辛时应根据患者生理、病理状况以及药物相互作用,及时监测血药浓度,并根据监测数据和影响因素调整给药方案,实施个体化给药.     

303例地高辛血浆浓度监测分析

地高辛为中速强心类药物，广泛用于治疗各种急慢性心功能不全及室上性心动过速，心房颤动和扑动，但其治疗指数低，治疗窗狭窄，毒付作用大，药动学及药效学个体差异大，常规剂量亦可导致中毒或达不到疗效，因此对其进行血药浓度监测已作为调整给药方案，保持有效血药浓度及预防中毒的有效手段。作自2003年8月至2005年6月对303例患血浆地高辛浓度监测结果进行回顾性分析，以便给临床用药提供参考。     

地高辛治疗老年人心血管相关疾病的临床研究

目的研究影响血清地高辛浓度关键因素,为老年人患者提供更安全、个性化治疗方案。方法收集2013年12月到2015年4月495例老年患者的血清地高辛浓度数据,通过统计分析,研究地高辛血药浓度与患者性别、年龄及服用剂量等因素之间关系。结果在495例老年患者中,地高辛血药浓度在有效浓度范围0.5~2.0 mg/ml之间,占68.69%,出现中毒症状仅7例;地高辛血药浓度2.0 ng/ml时,占20.80%,出现中毒症状46例。地高辛血药浓度越高,中毒比率也明显升高。随着患者年龄增高,地高辛血药浓度也逐渐增高。高地高辛药物浓度在0.5 ng/ml和2.0 ng/ml的年龄分布上差异具有显著性(P0.05)。女性比男性地高辛血药浓度要高(1.32±0.56 mg/ml比1.21±0.97 mg/ml),但不同性别地高辛血药浓度分布差异无显著性(P0.05)。从剂量方面临床研究发现,高、中、低剂量组地高辛平均血药浓度分别为2.43±1.12 mg/ml、1.54±0.75 mg/ml和0.86±0.43 mg/ml。血药浓度是随着服用的药物剂量而增加的。结论地高辛血药浓度在不同个体之间存在明显差异,因此需要考虑多种影响因素。对于大多数患者,地高辛药物服用剂量应不大于0.15 mg/d,而女性地高辛服药量应该适当减少。对地高辛血药浓度进行监测,有助于更深入理解影响地高辛血药浓度关键因素,为老年人患者提供更合理治疗方案。     

91例心衰患者地高辛治疗的临床用药分析

地高辛在临床上是治疗充血性心力衰竭和快速性心房颤动的有效药物,因其疗效指数低,安全范围窄,个体差异大,治疗量与中毒量在一定程度上相互重叠的药动学特性,是临床治疗药物需作血药浓度监测的主要品种之一[1].实践工作中认识到,临床药学部门为医生提供血药浓度数据结果是不够的.如何正确评价血药浓度与临床效果的关系,分析影响血药浓度的各种因素,协助医生对异常血药浓度患者实施药学监护下的个体化给药,有效预防地高辛的不良反应,积极救治中毒患者,才是临床药学工作者必须面对的实际问题[2].本文对91例临床使用地高辛的患者病情及血药浓度进行回顾性分析.     

105例地高辛血药浓度监测及意义

目的检测地高辛血药浓度,为临床安全、有效、合理使用地高辛提供参考依据。方法调查该院2010年3～11月检测的105例患者地高辛血药浓度监测数据,并分析个体差异及年龄对地高辛血药浓度的影响。结果低于治疗范围1.0～2.6nmol/L低限者即小于1.0nmol/L的有25例患者,均未出现中毒症状;在有效治疗浓度范围内共70例患者中有6例出现中毒症状,占8.57%,高于治疗范围的共10例患者中有7例出现中毒症状,占70%;105例检测结果中共13例出现中毒症状,占监测例数的12.38%。中毒的临床表现以心律失常和消化道反应为主;中毒原因除个体差异外有合并用药、血肌酐增高、高血钾等。结论地高辛血药浓度监测能较好地反映地高辛临床疗效,指导临床及时增减药量,因个体差异较大,地高辛浓度正常不能排除药物中毒的可能性,老年患者及合并用药患者是临床监测的重点。     

地高辛在临床治疗中的合理应用

临床应用地高辛治疗心力衰竭(心衰)及控制快速心室率已有200多年的历史,并成为治疗心衰的主要药物之一,但因其治疗指数低,安全范围窄,个体差异大,影响因素多,是临床治疗药物中最主要的监测品种。我们在2000~2005年的5年间对临床使用地高辛的患者进行血药浓度监测,结果显示中毒率达14.46%,分析发现中毒病例大多是因给药剂量和给药方法不当造成[1]。为了提高地高辛临床治疗效果,避免中毒等不良反应事件的发生,我们从以下几方面探讨地高辛在临床治疗中的合理应用。1重视药动学、药效学特点1·1地高辛的生物利用度及给药时间地高辛口服生物利用…     

地高辛血药浓度监测221例结果分析

目的:分析影响地高辛血药浓度的因素。方法:对我院221例患者进行地高辛血药浓度测定并进行结果分析。结果:在221例监测结果中,56例(25.34%)血药浓度低于0.50 ng·mL-1,115例(52.04%)血药浓度在0.5～2.0 ng·mL-1之间,50例(22.62%)血药浓度高于2.0 ng·mL-1。患者血药浓度与年龄相关(P<0.01),与性别无关(P>0.05),联合用药对患者血药浓度有一定影响。结论:地高辛血药浓度个体差异大,应重视地高辛血药浓度监测,制定安全合理的个体化治疗方案。     

280例地高辛血药浓度监测结果与分析

目的 对北京军区总医院2007年5月至2009年4月两年间地高辛血药浓度监测情况进行总结分析,旨在为临床合理用药提供药学技术服务。方法采用荧光免疫偏振法（FPIA）监测地高辛血药浓度,对280例次血药浓度监测结果进行比较分析。结果以0．8～2．0ng·ml^-1为地高辛安全有效血药浓度。280例次地高辛血药浓度测定值在安全有效浓度范围162例次（占57．9％）,低于此浓度范围下限（〈0．8ng·ml^-1）86例次（占30．7％）,高于安全有效浓度范围上限（〉2．0ng·ml^-1）32例次（占11．4％）。结论影响地高辛血药浓度及疗效的因素众多且复杂,本资料约40％的血药浓度未在安全有效范围之内,因此临床使用地高辛时应注意患者生理、病理状况及药物相互作用,及时监测血药浓度并根据监测数据和影响因素调整给药方案,实现给药个体化,安全有效地使用地高辛。     

老年患者地高辛血药浓度监测及影响因素分析

目的:通过对我院2004年9月至2005年4月老年患者的地高辛血药浓度监测结果进行回顾性的统计分析,促进我院临床用药水平的提高。方法:采用荧光偏振免疫法(FPIA)测定地高辛血药浓度,并对监测结果和影响因素进行分析。结果:老年患者地高辛血药浓度个体差异大,在有效血药浓度范围内也易发生中毒。结论:应当常规进行地高辛血药浓度监测,并结合临床症状和相关指标制定用药方案,实现用药的个体化,减少毒副反应,提高治疗效果。     

地高辛间歇疗法治疗窦性心律心力衰竭的疗效评价

目的:评价间歇疗法维持量地高辛治疗窦性心律心力衰竭的临床疗效。方法:100例窦性心律心力衰竭患者随机分为二组:A组50例采用间歇维持量地高辛治疗;B组50例采用持续维持量地高辛治疗。结果:两组患者治疗前与治疗3个月和6个月比较,左心室射血分数(LVEF)、心室率(HR)均有显著性差异,P<0.01。结论:间歇维持量地高辛疗法可降低洋地黄过量或中毒的发生率,其疗效相似,可做为一种安全有效的临床给药方法。     

Prospective Comparative Study of Variable Dosage and Variable Frequency Regimens for Administration of Gentamicin

In patients with impaired renal function, careful adjustment of gentamicin dosage is required to achieve therapeutic yet nontoxic concentrations. Two regimens that differ in pharmacodynamic characteristics have been recommended for this purpose: prolonging the intervals between administration of equal doses (variable frequency regimen [VFR]) or administering a loading dose followed at the usual intervals by reduced maintenance doses (variable dosage regimen [VDR]). These regimens were compared in a prospective, randomized study of 20 seriously ill hospitalized patients, 10 on VFR and 10 on VDR. Wide variability in peak serum levels of gentamicin was observed both between patients and in individual patients after separate injections of the same dosage. As predicted by the design of these regimens, the trough serum levels of gentamicin correlated significantly with the serum creatinine concentrations in patients on the VDR but not in patients on the VFR. A gentamicin trough level of ≥4 μg/ml was the only variable among those tested that correlated significantly with development or progression of renal insufficiency during treatment with gentamicin, but such trough levels were observed frequently on both regimens. Whereas this study does not permit a direct comparison of the therapeutic efficacy of VDR and VFR, no difference in the risk of nephrotoxicity with these regimens was observed.     

Digoxin-specific antibody fragments in the treatment of digoxin toxicity

Context. Digoxin-specific antibody fragments (digoxin-Fab) are widely regarded as a safe and effective treatment for the management of acute and chronic digoxin poisoning. Calculated equimolar doses of digoxin-Fab are high, very expensive, and infrequently used. Objective. To review the pharmacology, efficacy, effectiveness, indications, safety and the dosage of digoxin-specific antibody fragments. Methods. Pubmed, Embase, Medline and Cochrane were searched from 1946 to May 2013 using the terms digoxin, digoxin-specific Fab, and digoxin antibody. Pharmacology and kinetics of digoxin and digoxin-Fab. Digoxin acts via inhibition of Na⁺/K⁺ ATPase. It has a narrow therapeutic index. Digoxin has 60–80% bioavailability, a mean plasma half-life of 40 h and a volume of distribution (Vd) of 5–10 L/kg and low protein binding (20%). A 40-mg vial of digoxin-Fab (DigiFab) binds 0.5 mg digoxin. Digoxin-Fab has a mean plasma half-life of 19–30 h and a Vd of 0.4 L/kg. The half-lives of both digoxin and digoxin-Fab are prolonged in renal failure to over 100 h. Efficacy and effectiveness of digoxin-Fab. There were no randomised clinical trials examining the use of digoxin-Fab for acute or chronic digoxin poisonings. Ten case series with a total of 2,080 patients have reported on the use of digoxin-Fab in digoxin poisoning. In three large case series of 430 acute and 1308 chronic poisonings, response rates to digoxin-Fab vary from 80–90% to 50%. The time for reversal of digoxin toxicity is reported to be 30–45 min. Studies with pharmacokinetic data showed that free digoxin concentration fell to almost zero within a few minutes following the administration of digoxin-Fab. Digoxin-Fab was used more frequently in acute than chronic digoxin poisoning with a higher reported success rate when used in acute overdose. It is sometimes recommended to use full neutralisation doses (based on serum concentration × Vd or ingested dose). It has also been proposed to use half this dose. Indications for digoxin-Fab. Patients who have life-threatening tachy–bradyarrhythmias, hyperkalaemia (> 6 mmol/L) or haemodynamic instability with an elevated digoxin concentration (> 2 μg/L or 2.6 nmol/L). The lowest effective digoxin-Fab dosing regimen has not been established. Safety of digoxin-Fab. Adverse events such as exacerbation of heart failure, increased ventricular rate and hypokalaemia are uncommon (< 10%). Recrudescence of digoxin toxicity and allergic reactions are infrequent. Digoxin-Fab dosing in acute poisoning. Digoxin load based on ingested dose will generally overestimate digoxin-Fab doses as bioavailability is 60–80%, and further reduced by vomiting and activated charcoal. Digoxin load based on concentration also will be overestimated when the concentration is taken before distribution is complete (around 6 h). Much smaller doses of digoxin-Fab can eliminate the digoxin in the central compartment (Vd ≈ 55 L). In imminent cardiac arrest, it may be justified to give a full neutralising dose. Otherwise, based on pharmacokinetic modelling, it is recommended to give 80 mg bolus digoxin-Fab, repeated as required according to clinical parameters because the onset of clinical response is usually rapid. Most patients would be expected to require a total of less than half of the calculated neutralising dose using this strategy. Digoxin-Fab dosing in chronic poisoning. Even if digoxin load is estimated following distribution (> 6 h), excessive neutralisation doses may still be calculated because of variation in Vd due to equations failing to account for lean body weight, age and renal failure. In practice, it is suggested to give 40 mg (1 vial) digoxin-Fab at a time and repeat after 60 min if patient is still symptomatic, sooner if patient is clinically unstable. In general, 40–120 mg (1–3 vials) should be sufficient. Conclusions. Digoxin-Fab is safe and indicated in all patients with life-threatening arrhythmias and an elevated digoxin concentration. However, calculated full neutralising doses of digoxin-Fab are expensive and may not be required. In acute poisoning, a small bolus of 80 mg, repeat if necessary, titrated against clinical effect, is likely to achieve equivalent benefits with much lower total doses. With chronic poisoning, it may be simplest to give 40 mg (1 vial) digoxin-Fab at a time and repeat after 60 min if there is no response.     

Quinidine saliva concentrations: absence of correlation with serum concentrations at steady state

Serum and saliva quinidine concentrations were measured in eight subjects with cardiac arrhythmias on various dosage regimens. There was good correlation between serum and saliva quinidine concentration after a single dose, but there was no such relationship after repeated dosing. Comparison of the area under a hysteresis loop, obtained by plotting the saliva/serum quinidine concentration ratio as a function of serum quinidine concentration over a dosing interval, indicated an exponential increase with increasing mean serum quinidine concentration. Salivary quinidine concentration predictions based on the Henderson-Hasselbalch equation did not correlate with the serum quinidine concentration under the steady-state conditions. These data suggest that quinidine concentration in saliva is not a direct reflection of its serum concentration in cardiac patients on maintenance (steady-state) therapy and hence not useful for therapeutic drug monitoring.     

Comparative efficacy of once versus twice daily mevinolin in the therapy of familial hypercholesterolemia

Mevinolin, a competitive inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, is an effective hypocholesterolemic agent in patients with primary hypercholesterolemia when given in a twice-daily regimen. The present study compares the hypocholesterolemic effects of mevinolin given in a twice-daily dosage regimen with the same total dosage given either once in the morning or once in the evening in 12 patients with heterozygous familial hypercholesterolemia. Ten patients took a total daily dose of 40 mg of mevinolin and two took 20 mg. On the twice-daily dosage regimen, plasma concentrations of total cholesterol decreased 29.5% and 35.9% as compared with 21.4% and 26.9% with mevinolin given once in the morning and 27% and 32.2% with the drug given once in the evening. These values are all significantly different from baseline, but differences between the three treatment regimens do not reach statistical significance (P = 0.07 for the twice-daily versus once-in-the-morning dosage regimens). We conclude that once-daily administration of mevinolin, particularly in the evening, is an effective hypocholesterolemic regimen in patients with familial hypercholesterolemia.     

Bladder training: its role in evaluating the effect of an antispasticity drug on voiding in patients with neurogenic bladder.

Fourteen patients with spinal cord damage were treated with Ba-34647 (Lioresal, Ciba-Geigy), a new antispasticity drug. The treatment was initiated for excessive skeletal muscle spasticity and voiding difficulty. Seven of the patients had been wearing indwelling catheters and seven were catheter-free. The former were given trials at voiding after removal of catheters; the usual assistive methods common to most bladder training regimens were administered. Despite this, the trials were unsuccessful in reducing residual urine to acceptable levels. With addition of therapeutic doses of the drug without the training regimen, voiding trials were also unsuccessful excepting the response of one patient. The drug plus the training regimen was effective in reducing residual urine to acceptable levels in all patients. On discontinuing or decreasing the dosages of the drug, there was gradual but rapid build-up of residual urine despite the active training regimen. Restoration of effective dosage again led to satisfactory voiding function in all patients. The catheter-free group suffered from frequency, nocturia, and bed-wetting owing to excessive residual urine despite the employment of active training regimens. With addition of optimal dosages of Ba-34647, these problems were markedly reduced. They increased with drug discontinuation or dosage decrease and again improved upon restoration of effective doses. Bladder training, including active assistance to the expulsion of urine, is essential to the evaluation of antispasticity drugs for their effect on voiding.     

Initial dosage regimens of gentamicin in patients with burns

For 95 patients with burns the gentamicin dosage regimen necessary to achieve optimal serum concentrations was determined. Individual elimination rates and distribution volumes for gentamicin were determined and correlated with renal function parameters and age. In patients with burns who had normal serum creatinine levels (less than 1.5 mg/dl), gentamicin clearance and thus dosage regimens can be stratified by age. Gentamicin's clearance decreased inversely with age. Initial dosage guidelines were calculated for different age groups of patients with normal levels of serum creatinine. The guidelines were developed to assist the clinician in attaining therapeutic concentrations with initial doses of gentamicin. Therapeutic serum concentrations were reached in most patients with burns dosed by these guidelines. Serum gentamicin concentrations should always be monitored during therapy, and dosages should be adjusted to ensure optimal concentrations during the course of therapy.     

Optimal treatment schedule of meropenem for adult patients with febrile neutropenia based on pharmacokinetic–pharmacodynamic analysis

The objectives of this study were to develop a population pharmacokinetic (PK) model of meropenem, to simulate the percent time above minimum inhibitory concentration (%T > MIC) at various MICs, and to estimate effective dosage regimens by calculating the target attainment rates against various strains of bacteria. A total of 209 plasma samples (1–3 concentrations per patient) were obtained from 98 adult Japanese patients with febrile neutropenia in an open-labeled Phase 3 study. The final population PK model was fit to a two-compartment model with zero-order input. Creatinine clearance had a positive significant correlation with CL. Gender had a significant effect on Vc; however, this effect was small, and the PK profile in male patients was similar to that in female patients. The population PK parameters developed in this study are useful in simulating PK profiles of meropenem at various dosage regimens precisely for calculation of %T > MIC. The PK–PD analysis indicated that 0.5 g every 6 h (q6h) was more effective than 1 g q12h, although provided 2 g per day in total. A meropenem dosage regimen of 1 g q8h and/or longer infusion duration was better against a pathogen of comparatively low sensitivity, Pseudomonas aeruginosa (for MIC ≥2 μg/ml). Although causative bacteria were identified in a small number of patients, the target attainment rates at 75%T > MIC (89%) were comparable to microbiological response (89%). The present PK–PD analyses under various conditions are useful in the treatment of febrile neutropenia.     

不同衰弱评分下老年多发性骨髓瘤患者化疗疗效及安全性的评估

目的:比较老年多发性骨髓廇(MM)患者不同衰弱评分下不同化疗方案的疗效及安全性。方法:回顾性分析老年MM患者的临床资料,包括年龄、治疗方案、疗效、不良反应以及衰弱评分,包含日常生活能力评分、日常生活活动能力量表及Charlson合并症指数,按照评分标准将患者分为身体状态良好、欠佳及虚弱3组。统计分析不同体质状况的老年MM不同化疗方案的治疗有效率、1年总生存率及不良反应发生率。结果:70例患者中,身体状态良好、欠佳和虚弱组的治疗有效率分别为79.5%、81%和40%。良好患者中二联组和三联组的有效率分别为54.5%、89.3%,欠佳患者中分别为70%、90.9%,虚弱患者中为42.9%和33.3%,良好患者中三联方案优势明显,较二联方案差异有统计学意义(P<0.05),而欠佳患者和虚弱患者二联、三联化疗方案疗效差异不显著。在硼替佐米诱导期间,三联组的不良反应发生率(78.6%)高于二联组(67.9%),但比较差异无统计学意义(P>0.05),各组间1年总生存率及伴有分子遗传学异常的MM患者选用不同治疗方案的疗效无明显差异。结论:疗效与患者的体质状况相关,对于体质良好的患者,应...