环孢素给药后2 h血药浓度在器官移植中的作用

目的：环孢素A的微乳剂型新山地明作为最重要的免疫抑制剂之一，已在肾脏、心脏、肝脏、肺脏等器官移植中广泛应用，探讨如何监测环孢素血药浓度以调整最佳用药量并将毒副作用降至最低。资料来源：应用计算机检索Pubmed 1992—01／2001—12有关器官移植中环孢素血药浓度监测的文献，检索词“cyclosponne A，therapuetic drug monitoring”，并限定文章语言种类为English。资料选择：对检索到的文献进行粗筛，选择与环孢素血药浓度监测相关的信息进行整理，选取针对性强的文章。资料提炼：共检索到有关环孢素血药浓度监测的文献40余篇，11篇文献符合纳入标准。资料综合：环孢素A的谷值血药浓度与浓度-时间曲线下面积的相关性无显著性，而给药后2h血药浓度与浓度-时间曲线下面积的相关性最好。给药后2h时血药浓度变异系数小，它的变化对浓度-时间曲线下面积影响最大。结论：推荐监测器官移植患者环孢素A给药后2h血药浓度变化替代谷值血药浓度，防止因环孢素用药不当出现急性排斥反应或药物中毒。     

某胸科医院272名护士抗结核药物血药浓度监测知信行水平分析

目的 探讨某胸科医院护士抗结核药血药浓度监测的认知、态度、行为现状。方法 采用便利抽样法,于2018年9月选取西安市胸科医院的272名临床护士作为调查对象。采用自行设计的抗结核药物血药浓度检测知信行调查问卷,对其进行调查。结果 本组胸科医院临床护士抗结核药物血药浓度监测认知得分（74.15±15.13）分,正确率为74.15%;抗结核药物血药浓度监测态度得分（43.04±4.21）分;抗结核药物血药浓度行为得分（41.18±3.29）分。不同学历、工作年限的胸科医院临床护士,其抗结核药物血药浓度监测认知得分比较,差异均有统计学意义（P<0.05）;不同年龄、职称、工作年限的胸科医院临床护士,其抗结核药物血药浓度监测行为得分比较,差异均有统计学意义（P<0.05）;不同职称的护士,其抗结核药物血药浓度监测态度得分比较,差异有统计学意义（P<0.05）。结论 本组胸科医院临床护士抗结核药物血药浓度监测的认知处于中等以上水平、态度及行为得分均处于较高水平;护理管理者应重视对护士抗结核药血药浓度监测认知、态度、行为的培训和管理,以推进血药浓度监测工作的进一步开展。     

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.     

重症感染患者美罗培南血药浓度达标情况及影响因素分析

目的 分析美罗培南血药浓度达标情况及可能的影响因素,为优化重症感染患者美罗培南的给药方案提供依据。方法 采用回顾性研究方法,收集广西南宁市第一人民医院2020年5月至2022年2月使用美罗培南并进行血药浓度监测的重症感染病例资料185例,以谷浓度2μg/ml为靶值,将患者分为达标组113例和未达标组72例,统计美罗培南谷浓度的达标情况并分析其影响因素。结果 185例重症感染患者美罗培南的谷浓度中位数为3.41μg/ml,血药浓度达标率为60.44%,单因素分析显示,达标组和未达标组患者的年龄、给药剂量、肌酐清除率差异有显著性（P<0.05）。多因素logistic回归分析显示,肌酐清除率是美罗培南血药浓度达标率的影响因素。结论 重症感染患者美罗培南血药浓度达标率较低,建议加强血药浓度监测,以优化美罗培南的给药方案,提高临床疗效,减少不良反应及耐药菌的产生。     

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。     

中国成人万古霉素给药剂量的商榷

目的探讨中国成人万古霉素每日2g给药方案，能否达到10--20mg／L的目标血药浓度。方法回顾性分析交通大学医学院附属瑞金医院2011年9月至2012年12月收治的使用万古霉素且进行血药浓度监测的122例住院患者临床资料，分析给药剂量、年龄、性别、体重、合并用药等与血药谷浓度的相关性。结果按说明书给药的患者中，62．1％血药谷浓度低于目标血药谷浓度。年龄是患者用药后血药浓度是否能够达到目标值的独立危险因素，对于符合说明书剂量给药的患者，年龄〈60岁者中70．0％低于目标血药浓度；年龄≥60岁者中，62．5％达到或高于目标血药浓度。结论临床医师和药师需审慎地评估患者的给药剂量，尤其应该考虑年龄的独立影响因素。     

血药浓度监测下癫痫的多药改为单药治疗的研究

目的 观察在血药浓度监测下由多药改为单药治疗癫痫的疗铲。方法 监测30例血药浓度,所有患者均出现1种以上血药浓度不足或过量,经减药或单用苯妥英钠、丙戊酸钠、卡马西平。结果 8例发作消失,7例发作减少75％以上,4例减少发作50％以上;6例发作频率无变化,但发作程度减轻;5例发作频率增加,拒绝减药治疗。结论 单药应用效果满意,但应进行血药浓度监测。     

地高辛血药浓度监测200例次及分析

地高辛(digoxin)为强心苷类药物,是临床治疗充血性心力衰竭和控制快速性心房颤动、心房扑动的心室率等的常用药物,由于其治疗安全范围小,个体差异大,故临床需对其进行血药浓度监测,以调整给药方案,为医生安全、合理用药提供依据[1].作者自2010年1月至10月选择本院应用地高辛200例病例就其血药浓度监测结果进行统计分析.报道如下.     

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。     

肾移植后环孢素A浓度监测及其影响因素

背景:对使用环孢素A的患者进行长期、定期的血药浓度监测以做到个体化给药具有非常重要的临床意义。目的:总结肾移植后环孢素A血药浓度监测方法及影响其血药浓度的因素,以期为临床安全有效地使用环孢素A提供参考。方法:以"环孢素A、肾移植、血药浓度、影响因素"及"Cyclosporin A,Renal Transplantation,blood drug level"为关键词,采用计算机检索2000-01/2012-01相关文章。纳入肾移植后应用环孢素A进行免疫抑制治疗,并对其血药浓度进行检测的文章及有关环孢素A检测方法及影响环孢素A血药浓度因素的文章;排除重复研究或Meta分析类文章。共纳入30篇相关文献进行综述。结果与结论:由于环孢素A的治疗窗较窄,生物利用度相差较大,一般的给药方案是首次剂量依据体质量给予,此后则参考环孢素A的测定浓度及时进行剂量调整。目前主要采用荧光偏振免疫法及高效液相色谱法对其血药浓度进行检测,同时可应用人工神经网络对其进行预测。当然在调整给药剂量的同时还要考虑一些药物相互作用及患者自身病理生理因素的影响。肾移植后患者必须在其治疗过程中常规性监测环孢素A血药浓度,避免出现环孢素A血药浓度过大或不足,同时综合考虑临床各方面的因素,及时调整患者的用药情况,实施个体化用药方案,使肾移植后患者能获得最佳治疗效果。     

Vigabatrin: a novel therapy for seizure disorders

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of vigabatrin and its role in the management of seizure disorders. METHODS: A MEDLINE search of English-language literature from January 1993 through January 1999 was conducted using vigabatrin as a search term to identify pertinent studies and review articles. Additional studies were identified from the bibliographies of reviewed literature. The manufacturer provided postmarketing surveillance data. Priority was given to randomized, double-blind, placebo-controlled studies. FINDINGS: Vigabatrin is a selective and irreversible inhibitor of gamma-aminobutyric acid transaminase. In controlled clinical trials of vigabatrin add-on therapy in patients with uncontrolled partial seizures, 24-67% of patients achieved a < or =50% reduction in seizure frequency. Data from two comparative trials with carbamazepine monotherapy indicate that vigabatrin monotherapy reduces the frequency of partial seizures in patients with newly diagnosed epilepsy. Vigabatrin also controls infantile spasms, particularly those associated with tuberous sclerosis. Vigabatrin is more effective in patients with partial seizures than in those with generalized seizures. The drug is generally well tolerated. Headache and drowsiness were the most common adverse effects observed in controlled clinical trials; visual field defects, psychiatric reactions, and hyperactivity also have been reported. There are no known clinically significant drug interactions. CONCLUSIONS: Vigabatrin improves seizure control as add-on therapy for refractory partial seizures and may produce therapeutic benefits in the treatment of infantile spasms. Vigabatrin is generally well tolerated, with a convenient administration schedule, a lack of known significant drug interactions, and no need for routine monitoring of plasma concentrations.     

Kindling as a model of drug-resistant partial epilepsy: selection of phenytoin-resistant and nonresistant rats.

Complex partial seizures comprise the major uncontrolled seizure type in adult patients with epilepsy. Any improvement of our understanding of the mechanisms through which these seizures are often refractory to antiepileptic drugs is therefore of considerable importance. By examining the effects of the anti-epileptic drug phenytoin in a large group of kindled rats, a widely used model of complex partial seizures, animals with different sensitivity to this drug were selected. Using determination of the focal seizure threshold for evaluation of phenytoin's anticonvulsant effect, most animals (about 60%) showed variable effects in response to phenytoin. However, about 20% of the animals ("phenytoin nonresponders") showed no increase in their focal seizure threshold at repeated test trials with phenytoin, and 20% ("phenytoin responders") exhibited reproducible increases in focal seizure threshold after injection of phenytoin. Phenytoin responders and nonresponders thus selected were used for subsequent experiments. The different response of focal seizures to phenytoin was not related to differences in pharmacokinetics or location of the stimulating electrode. Although phenytoin reproducibly increased the threshold for induction of afterdischarges in responders, it did not alter severity or duration of the elicited seizure response. In contrast to phenytoin, carbamazepine induced increases in focal seizure threshold in all kindled rats. Duration of seizures and afterdischarges were significantly reduced by carbamazepine in phenytoin responders, but not in nonresponders, although plasma levels of carbamazepine were the same in both groups. The difference in response of kindled rats to phenytoin was restricted to kindled seizures, because phenytoin induced the same anticonvulsant effect on the threshold for generalized tonic electroconvulsions (determined via transauricular electrodes) in both groups of kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved sexual function in three men taking lamotrigine for epilepsy

Little information exists about the effects of newer antiepileptic drugs (AEDs) on sexual function in men with epilepsy. We report a series of three male veterans whose sexual disorders improved with lamotrigine. All three had partial seizures. One patient was taking phenobarbital and gabapentin and complained of decreased potency and anorgasmia. After lamotrigine was added for better seizure control and the dosage of gabapentin was tapered, anorgasmia improved. The second patient complained of impotence after a rash while taking phenytoin and carbamazepine. Impotence persisted with phenobarbital, valproate, and gabapentin. Eight months after gabapentin was replaced with lamotrigine, impotence improved. The third patient complained of long-standing impotence. Treatment with five AEDs had no effect on the dysfunction. Lamotrigine was added to the carbamazepine regimen; impotence improved with decrease in carbamazepine and increase in lamotrigine. The favorable effect of lamotrigine on sexual disorders in these three patients suggests this drug should be considered under appropriate circumstances for men who have sexual dysfunction while taking other antiepileptic agents.     

Oxcarbazepine, an antiepileptic agent

BACKGROUND: Epilepsy is a common neurologic condition. Many of the currently approved pharmacologic agents for its treatment are associated with numerous adverse drug reactions and drug interactions. OBJECTIVE: This review describes the pharmacology and therapeutic use of oxcarbazepine, an analogue of the well-known antiepileptic agent carbamazepine. METHODS: Articles for review were identified through a search of MEDLINE, International Pharmaceutical Abstracts, and EMBASE for the years 1980 through 2000. The terms used individually and in combination were oxcarbazepine, carbamazepine, epilepsy, and seizures. RESULTS: Oxcarbazepine and its primary metabolite have been effective in animal models of epilepsy that generally predict efficacy in generalized tonic-clonic seizures and partial seizures in humans. The exact mechanism of action of oxcarbazepine is unknown, although as with carbamazepine, it is believed to involve blockade of voltage-gated sodium channels. The pharmacokinetic profile of oxcarbazepine is less complicated than that of carbamazepine, with less metabolism by the cytochrome P450 system, no production of an epoxide metabolite, and lower plasma protein binding. The clinical efficacy and tolerability of oxcarbazepine have been demonstrated in trials in adults, children, and the elderly. In a double-blind, randomized, crossover trial in adults, oxcarbazepine 300 mg was associated with a decrease in the mean frequency of tonic seizures (21.4 vs 30.5 seizures during steady-state periods) and tonic-clonic seizures (8.2 vs 10.4) compared with carbamazepine 200 mg (P = 0.05). A multinational, multicenter, double-blind, placebo-controlled, randomized, 28-week trial assessed the efficacy and tolerability of oxcarbazepine at doses of 600, 1200, and 2400 mg as adjunctive therapy in patients with uncontrolled partial seizures. All 3 oxcarbazepine groups demonstrated a reduction in seizure frequency per 28-day period compared with placebo (600 mg, 26% reduction; 1200 mg, 40% reduction; 2400 mg, 50% reduction; placebo, 7.6% reduction; all, P < 0.001). A trial in children assessed the efficacy and toxicity of oxcarbazepine (median dose, 31.4 mg/kg/d) as adjunctive therapy for partial seizures. Patients receiving oxcarbazepine experienced a 35% reduction in seizure frequency, compared with a 9% reduction in the placebo group (P < 0.001). The most common adverse effects associated with oxcarbazepine are related to the central nervous system (eg, dizziness, headache, diplopia, and ataxia) and the gastrointestinal system (eg, nausea and vomiting). Compared with carbamazepine, there is an increased risk of hyponatremia with oxcarbazepine. The frequency and severity of drug interactions are less with oxcarbazepine than with carbamazepine or other antiepileptic agents. CONCLUSIONS: Oxcarbazepine may be considered an appropriate alternative to carbamazepine for the treatment of partial seizures in patients who are unable to tolerate carbamazepine. Its use in nonseizure disorders remains to be examined in large-scale clinical trials, and pharmacoeconomic comparisons of oxcarbazepine with other antiepileptic agents, particularly carbamazepine, are needed.     

Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy

OBJECTIVE: To describe a patient in whom we used adjunctive verapamil therapy was used for its P-glycoprotein inhibitory effects. CASE SUMMARY: Verapamil was added to the antiepileptic drug regimen of a 24-year-old woman with intractable epilepsy. The average time interval between hospitalizations for complex partial status doubled. The addition of verapamil greatly improved overall seizure control and subjective quality of life in this pharmacoresistant patient. DISCUSSION: The overexpression of P-glycoprotein in the central nervous system may be one mechanism of pharmacoresistance in patients with epilepsy. The calcium-channel blocker verapamil is a known inhibitor of P-glycoprotein and may function to block P-glycoprotein-modulated efflux of antiepileptic drugs in the brain, thereby raising the intracellular concentration of antiepileptic drugs and ultimately decreasing seizure burden in patients with refractory epilepsy. CONCLUSIONS: Verapamil may offer pharmacoresistant patients hope of improved seizure control due to its potential P-glycoprotein inhibitory effects.     

脑梗死后继发性癫痫51例临床分析

目的探讨脑梗死后继发癫痫的临床特点。方法回顾性分析51例脑梗死后癫痫患者的临床特点,比较癫痫发作时间、发作类型与脑梗死部位的关系。结果脑梗死患者皮质病变者38例（74．51％）,皮质下病变者13例（25．49％）;脑梗死后癫痫急性症状性发作22例（43．13％）,其中继发全面性发作18例,部分性发作4例;迟发性癫痫29例（56．86％）,其中继发全面发作14例,部分性发作15例;继发全面发作组病灶位于皮层处23例,皮层下9例;部分发作组病灶位于皮层处11例,皮层下8例,2组比较差异无统计学意义（P〉0．05）。结论脑梗死后癫痫急性症状性发作以继发全面发作为主,迟发癫痫以部分发作为主;部分发作及继发全面发作均以皮层病变多见。     

Clinical pharmacology and therapeutic use of the new antiepileptic drugs

Although older generation antiepileptic drugs (AEDs) such as carbamazepine, phenytoin and valproic acid continue to be widely used in the treatment of epilepsy, these drugs have important shortcomings such as a highly variable and nonlinear pharmacokinetics, a narrow therapeutic index, suboptimal response rates, and a propensity to cause significant adverse effects and drug interactions. In an attempt to overcome these problems, a new generation of AEDs has been introduced in the last decade. Compared with older agents, some of these drugs offer appreciable advantages in terms of less variable kinetics and, particularly in the case of gabapentin, levetiracetam and vigabatrin, a lower interaction potential. Lamotrigine, topiramate, zonisamide and felbamate protect against partial seizures and a variety of generalized seizure types, vigabatrin is effective against partial seizures (with or without secondary generalization) and infantile spasms, while the use of oxcarbazepine, tiagabine and gabapentin is mainly restricted to patients with partial epilepsy (and, in the case of oxcarbazepine, also primarily generalized tonic-clonic seizures). Levetiracetam, the latest AED to be introduced, has been found to be effective in partial seizures, but its potentially broader efficacy spectrum remains to be determined in clinical studies. Currently, the main use of new generation AEDs is in the adjunctive therapy of patients refractory to older agents. However, due to advantages in terms of tolerability and ease of use, some of these drugs are increasingly used for first-line management in certain subgroups of patients. Due to serious toxicity risks, felbamate and vigabatrin should be prescribed only in patients refractory to other drugs. In the case of vigabatrin, however, first line use may be justified in infants with spasms.     

Intractable partial epilepsy: evaluation and treatment

Partial (focal or localization--related) epilepsy is the most common seizure disorder encountered in patients with epilepsy. These seizures are focal at onset-that is, emanating from a localized region of the brain. Patients with partial epilepsy may have seizures that are refractory to antiepileptic drug medication. The financial burden for these patients includes the cost of medical care and often the loss of employment. Psychosocial deterioration may be progressive as long as the seizures are intractable. Management includes confirmation of the type (or types) of seizures, exclusion of an intracranial epileptogenic lesion, and use of appropriate antiepileptic drug therapy. Referral of affected patients to a comprehensive epilepsy center for possible surgical treatment and investigational drug studies should be considered. In the care of the patient with intractable partial epilepsy, the goals should be to render the patient free of seizures and to allow the patient to become a participating and productive member of society.     

Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy

BACKGROUND: The efficacy of topiramate (TPM) as an adjunctive treatment for epilepsy has been established in placebo-controlled clinical trials. Clinical trials of antiepileptic monotherapy usually evaluate low and high doses of study drug or compare study drug with another active agent. OBJECTIVE: This article reviews available evidence for the use of TPM as monotherapy in patients with newly or recently diagnosed epilepsy. METHODS: A search of MEDLINE, EMBASE, BIOSIS, SCISEARCH, and the Cochrane Database of Systematic Reviews (all years) for reports of controlled trials of TPM monotherapy in patients with recently diagnosed (within the previous 3 years) epilepsy was conducted in January 2008 using the terms topiramate, epilepsy, newly diagnosed, recently diagnosed, and monotherapy. Identified trials were included in the review if they were published in peer-reviewed journals and enrolled > or = 20 patients. RESULTS: Three randomized, double-blind, controlled trials met the criteria for inclusion in the review. In a comparison of TPM 50 and 500 mg/d, the higher dose was associated with significantly greater freedom from seizures at 6 months compared with the lower dose (54% vs 39%, respectively; P = 0.02). The time to first seizure was significantly associated with mean plasma TPM concentrations (P = 0.015). In a comparison of TPM 50 and 400 mg/d, the time to first seizure was significantly longer with the higher dose compared with the lower dose (P<0.001, Kaplan-Meier analysis), and the probability of 12-month seizure freedom was significantly higher (76% vs 59%, respectively; P = 0.001). Again, the time to first seizure was significantly associated with mean plasma TPM concentrations (P = 0.029). In a comparative study of TPM 100 and 200 mg/d, carbamazepine 600 mg/d, and valproate 1250 mg/d, there was no significant difference in rates of 6-month seizure freedom with TPM 100 and 200 mg/d (49% and 44%, respectively), carbamazepine (44%), and valproate (44%). Adverse events in the 3 studies were similar between TPM dose groups, although the incidence generally increased with increasing doses, occurred early in treatment, and decreased with prolonged therapy. In a pooled analysis of the 3 trials, the most commonly occurring adverse events during dose titration were paresthesia (25%), fatigue (16%), dizziness (13%), somnolence (13%), and nausea (10%); the most frequent adverse events during maintenance therapy were headache (20%), decreased appetite (11%), and weight loss (11%). CONCLUSION: In the 3 studies reviewed, TPM monotherapy was effective and generally well tolerated in patients with newly diagnosed epilepsy.