老年人的药代动力学特点

老年人不仅患病率高，而且往往同时患有多种疾病，治疗时应用药物品种也较多，约有25％的老年患者同时使用4～6种药物，个别老年人甚至多至10种以上，因此发生药物不良反应的机率也随之增高。在给老年人用药时，应了解老年人的生理功能及药物代谢动力学的改变对药物作用的影响，才能制订合理的用药方案，确保安全有效的用药。     

老年人药代动力学的特征及一般用药原则

人类寿命在延长 ,不论在国内或国外 ,老年人口比例正在显著增加 ,按我国人口近期的统计 ,我国老年人口 2 0 0 0年已达 1 3亿多。人老病多 ,服药亦多。有报道约有 1/4老年人同时服用 4～ 6种药物 ,这都可引起老年人对药物副作用 (ａｄ ｖｅｒｓｅｄｒｕｇｓｒｅａｃｔｉｏｎ ,ＡＤＲ)的发生率增高。老年人的ＡＤＲ发生率比年轻人约高 2～ 3倍或更多 ,其症状多重且不典型 ,可被患者或医生们所疏忽或误诊。ＡＤＲ的发生与药代动力学密切相关。影响老年人药物治疗的因素 ,往往是多方面的 ,如 :①年龄、生理变化的影响 ;②疾病不同病程的存在 ;③…     

老年人药物代谢动力学特点

老年人药物代谢动力学特点牡丹江医学院抗衰老科学研究所（１５７０１１）吴景时广东省药物研究所药理研究室（５１０１８０）陈再智吴景时教授老年药物代谢动力学（ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓｉｎｔｈｅｔｈｅｅｌｄｅｒｌｙ）简称老年药动学，是研究老年机体对药...     

老年人抗菌药物药代动力学特点与临床应用

由于老年人组织器官功能减退,免疫防御能力下降,感染性疾病明显增多,尤其是严重的细菌感染,是导致死亡的重要原因之一。同时,由于老年人各器官功能衰退并伴有许多基础疾病,需要同时服用多种药物,药物代谢过程也发生了极大改变,老年人用药必须根据其自身药代动力学特点加以调整,并注意药物问相互作用。本文就老年人各系统、器官功能和病理生理的特征性改变对药物代谢的影响,抗菌药物在老年人的代谢变化,     

老年人药物效应动力学特点

老年人药物效应动力学特点上海铁道医学院药理学教研室（２０００７０）许士凯许士凯副教授药效学是药物效应动力学的简称，它是研究药物对机体的作用及作用机理的科学。老年药效学（ｐｈａｒｍａｃｏｄｙｎａｍｉｃｓｉｎｔｈｅｅｌｄｅｒｌｙ）改变是指机体效应器官对药...     

肝硬化患者利多卡因药代动力学变化

近年来,我们对肝硬化患者与正常人利多卡因及其代谢产物单乙基甘氨酸二甲苯胺（MEGX）的药代动力学进行了比较,旨在为临床用药提供依据。现报告如下。     

临床常用铜离子螯合剂药代动力学和不良反应研究进展

铜离子螯合剂能与铜离子发生螯合作用进而清除人体内过多的铜,临床常用于治疗威尔逊疾病。目前,国内对该类药物药代动力学的相关报道较少,且铜离子螯合剂在治疗过程中常出现不同类型、程度不一的不良反应。本文主要介绍这类药物的药代动力学和不良反应研究资料,为临床合理用药提供参考。     

老年人药物不良反应分析

由于老年人的生理学及药代动力学随年龄的增大而改变，特别是老年人一般合并有多种疾患，如高血压病、糖尿病、肿瘤等，往往应用的药物品种繁多，使得老年人出现药物不良反应(ADR)的机会增加，甚至因药源性疾病而住院治疗。因此，老年人应合理用药，避免药物不良反应的发生。     

替比夫定的药代动力学研究

目的评价中国健康志愿者单次口服不同剂量替比夫定的药代动力学特征以及多次给药后的稳态血浆药代动力学。方法42名年龄在18～40岁的健康志愿者,男32名,女10名,随机分配到200、400、600、800mg 4个剂量组。其中600mg剂量组受试者接受单剂量和多剂量的研究。多剂量每日给药,持续8d。采用HPLC-MS/MS法测定给药前和给药后不同时间替比夫定的主血浆、尿液药物浓度,并据此计算药代动力学参数。结果在单次口服200、400、600、800mg片剂后,受试者的达峰时间分别为2．50、2．00、2．00h和2．50h；半衰期的平均值分别为(43．3±15．2)h、(49．1±14．4)h、(39．4±12．1)h和(46．7±20．8)h；血药达峰浓度平均值分别为(1 753．2±389．0)ng/ml、(2 586．7±871．4)ng/ml、(3 703．6±1 219．0)ng/ml和(3 454．6±953．9)ng/ml；曲线下面积的平均值分别为(12 843．2±2 925．6)ng·h ~(1·)ml~1、(22 948．9±5 721．0)ng·~(1·)ml~1、(26 440．5±8 938．1)ng·h ~(1·)ml~1以及(28 820．9±7 912．9)ng·h ~(1·)ml~1；血浆清除率(600mg)为(6 545．6±1 504．4)ml/h；多次给药后的稳态药代动力学研究结果显示,在600mg/d的给药剂量下,连续给药8d后,平均稳态药时曲线下面积为(26 123．9±7 196．3)ng·h ~(1·)ml~1,平均血药浓度为(1 088．5±299．8)ng/ml,血药达峰浓度和曲线下面积蓄积囚子分别为1．02±0．21和1．23±0．26。结论受试者口服替比夫定以后,吸收较为迅速,给药后的2～3h即达到峰值。在200mg至800mg剂量范围内,血浆中替比夫定的药代动力学参数均呈现出一定的规律。替比夫定在受试者体内有轻微蓄积。     

肾移植受者口服多剂霉酚酸酯的临床药代动力学特点

目的 :通过对汉族肾移植受者口服多剂霉酚酸酯 (MMF)后体内霉酚酸 (MPA)血浆浓度的检测 ,描述汉族肾移植受者MPA的药代动力学基本特点 ,探讨替代MPA药物曲线下面积 (MPA AUC)的药物浓度临床监测指标。　方法 :2 1例汉族首次同种异体尸肾移植患者 ,分别于术后第 3天、11天和 2 1天检测服药后不同时点静脉血MPA浓度 ,绘制MPA的药 时曲线 ,计算MPA AUC ,并随访至术后 90天 ,分析MPA AUC的特点和变化规律 ,寻找与MPA AUC相关性最好的单点MPA浓度。　 结果 :MPA AUC为 (31 2 2± 3 37)mg/ (L·h)。MPA药 时曲线部分呈双峰 (42 86 % ) ,出现第一峰值时间 (TMAX1)为口服MMF后 (1 6 3± 0 73)h ,第一峰值 (CMAX1)为(8 5 9± 3 16 )mg/L ;出现第二峰值时间 (TMAX2 )为口服MMF后 (8 35± 3 72 )h ,第二峰值 (CMAX2 )为 (2 70± 1 6 0 )mg/L ;T1/ 2 为 (12 6 5± 8 18)h。与AUC相关性最好的单点MPA浓度为服药前浓度 (MPA C0 ) (R2 =0 6 2 0 4 ,P <0 .0 0 1)。　 结论 :汉族肾移植受者口服多剂MMF后MPA 药时曲线与白种人群的特点基本相符。服药前MPA浓度与AUC有良好相关性 ,可作为临床监测MPA浓度的指标。     

Characteristic features of folate-deficient neurological diseases in the elderly

Background:  Folic acid (folate) deficiency causes neurological disorders in aged people, the characteristic features of which were examined.
Methods:  Serum folate levels were determined in 343 neurological patients by chemiluminescence. We found 36 folate-deficient patients (10.5%) who were divided into elderly ≥ 65 years old (12 cases) and younger group, < 65 years old (24 cases), and were administered folate (15 mg/day) for 60 days.
Results:   Serum folate levels were not different between the elderly and younger group, while folate levels were lower in elderly females than elderly males. Neuropathy was more frequent in elderly male than elderly female patients. Elderly neurological patients with neuropathy more readily responded to folate supplementation than those without neuropathy. Folate-deficient patients with dementia were older than those without dementia, although nine younger patients had dementia and four of nine cases showed frontal dementia. Anemia or female sex was more frequent and neuropathy was less frequent among elderly patients with central nervous system involvement. Serum folate levels were lower in elderly anemic than nonanemic patients. Tube feeding was more frequent in elderly folate-deficient neurological patients than in younger ones. Folate therapy was less effective in elderly patients with dementia, although three cases improved. Elderly folate-deficient patients treated with tube feeding did not respond to the folate supplement.
Conclusion:   Folate deficiency was not rare among aged neurological patients, and its features were different from younger patients. Since folate-deficient neuroencephalopathies are responsive to folate supplementation in the elderly, the examination of elderly patients' serum folate level is valuable.     

老年心力衰竭病人地高辛药代动力学研究

目的研究老年心力衰竭（心衰）病人地高辛（ＤＧ）药代动力学变化规律及影响因素。方法用ＲＩＡ法测定ＤＧ血药浓度。用Ｂａｙｅｓｉａｎ一点法拟合ＤＧ个体药代动力学参数及给药方案。结果肌酐清除率（ＣＣｒ）５０．９±１６．４ｍｌ·ｍｉｎ－１／１．７３ｍ２，地高辛清除率（ＣＤＧ）６６．１±２３．４ｍｌ·ｋｇ－１／ｈ，分布容积（Ｖｄ）６．５１±０．９３Ｌ／ｋｇ，半衰期（Ｔ１／２）７７．９±２５．６ｈ，消除速度常数（Ｋ）０．００９９±０．００３３ｈ－１。年龄老化以及肾功能和心功能对地高辛药代动力学均有显著影响（Ｐ＜０．０５）。结论老年心衰病人的个体药代动力学参数波动范围大，个体差异更为突出，临床应在血药浓度监测的基础上实行最佳个体化给药。     

When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly

The age-related changes in the functions and composition of the human body require adjustments of drug selection and dosage for old individuals. Drug excretion via the kidneys declines with age, the elderly should therefore be treated as renally insufficient patients. The metabolic clearance is primarily reduced with drugs that display high hepatic extraction ('blood flow-limited metabolism'), whereas the metabolism of drugs with low hepatic extraction ('capacity-limited metabolism') usually is not diminished. Reduction of metabolic drug elimination is more pronounced in malnourished or frail subjects. The water content of the aging body decreases, the fat content rises, hence the distribution volume of hydrophilic compounds is reduced in the elderly, whereas that of lipophilic drugs is increased. Intestinal absorption of most drugs is not altered in the elderly. Aside of these pharmacokinetic changes, one of the characteristics of old age is a progressive decline in counterregulatory (homeostatic) mechanisms. Therefore drug effects are mitigated less, the reactions are usually stronger than in younger subjects, the rate and intensity of adverse effects are higher. Examples of drug effects augmented is this manner are postural hypotension with agents that lower blood pressure, dehydration, hypovolemia, and electrolyte disturbances in response to diuretics, bleeding complications with oral anticoagulants, hypoglycemia with antidiabetics, and gastrointestinal irritation with non-steroidal anti-inflammatory drugs. The brain is an especially sensitive drug target in old age. Psychotropic drugs but also anticonvulsants and centrally acting antihypertensives may impede intellectual functions and motor coordination. The antimuscarinic effects of some antidepressants and neuroleptic drugs may be responsible for agitation, confusion, and delirium in elderly. Hence drugs should be used very restrictively in geriatric patients. If drug therapy is absolutely necessary, the dosage should be titrated to a clearly defined clinical or biochemical therapeutic goal starting from a low initial dose.     

健康体检老年人心电图异常特征分析

目的观察老年人健康体检心电图的特征及相关因素,以明确老年人定期进行心电图检查的重要性。方法随机选取2010年1月-2013年6月参加健康体检的500例老年人,对其进行心电图检测,然后进行统计学分析。结果500例老年人中心电图异常总检出182例,总检出率为36．4％;男性和女性心电图异常检出率分别为39．2％和33．6％,男性检出率明显高于女性,差异有统计学意义（P〈0．05）。ST—T异常表现者在心电图异常者中占比最高（44．51％）,其次为传导阻滞（18．68％）及早搏（9．89％）等,且随年龄增大,所占比例呈现上升趋势（P〈0．01）：心电图异常特征与年龄、性别具有相关性。结论老年健康体检时进行心电图检测可以及早发现心电图异常者,老年人进行定期心电图检查对早期发现心血管疾病非常必要。     

The pharmacokinetics and effects of prochlorperazine in elderly female volunteers.

The pharmacokinetics and effects of prochlorperazine (PCZ) have been studied in six healthy elderly female volunteers in a double-blind placebo-controlled study of 3.125 mg intravenous (IV) and 25 mg oral PCZ. The pharmacokinetics of IV PCZ in elderly subjects appear similar to those previously obtained in young subjects, with a terminal half-life of 7.5 +/- 1.8 h after intravenous dosing. Oral bioavailability was low (14.7 +/- 1.5%). The pharmacological actions of prochlorperazine in elderly people appear to include antidopaminergic (prolactin rise) and anticholinergic (reduced salivary flow) effects. At the dose of PCZ used in this study, no significant haemodynamic or psychomotor changes were observed though there was a trend to prolongation of the movement component of the reaction time.     

国产舒芬太尼单次注射对老年手术患者药代动力学的影响

目的观察老年心血管手术患者国产舒芬太尼单次静脉注射的药代动力学特征。方法随机选择老年患者8例,ASAⅡ～Ⅲ级,年龄61～68〔平均(66.7±6.24)〕岁,体重62～78kg,平均(69.5±11.8)kg。全身麻醉后经前臂静脉注射舒芬太尼5μg/kg,于注药前和注药后1、3、5、10、20、30、60、120、180、240和360min采集肝素化血浆1ml注入真空试管中,-80℃低温保存待测。用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数:中心分布容积(Vc),表观分布容积(Vd),快速分布半衰期(t1/2π)、缓慢分布半衰期(t1/2α)、排除半衰期(t1/2β),常数(P、A、B、π、α、β)和速率常数(k12、k21、k13、k31、k10)、清除率(CL)和血药浓度与时间曲线下面积(AUC)等。结果老年人国产舒芬太尼的药代动力学符合三室开放模型,其三指数方程为:Cp(t)=21.58e-0.5046t+3.53e-0.0454t+0.21e-0.0029t。主要药代动力学参数t1/2π,t1/2α和t1/2β分别为(1.47±0.47)min、(15.91±3.02)min和(252.03±52.86)min;Vc和Vd分别为(0.255±0.134)L/kg和(10.072±4.236)L/kg;CL和AUC分别为(0.027±0.008)L.kg-1.min-1和(198.88±70.17)ng.ml-1.min-1。结论国产舒芬太尼在老年心血管手术患者的药代动力学符合三室开放模型,t1/2β明显延长,临床用药时需参考年龄因素减少剂量以减轻不良反应。     

An overview of the pharmacokinetics and pharmacodynamics of amlodipine in elderly persons with systemic hypertension

Pharmacokinetic and pharmacodynamic data were compared between elderly and young patients with hypertension who received single intravenous doses of amlodipine, a dihydropyridine calcium antagonist, followed by oral administration of amlodipine up to 10 mg once daily for 12 weeks. After intravenous administration, elderly patients had prolonged elimination half-life values (58 ± 11 vs 42 ± 8 hr; p < 0.05) caused by decreased clearance (19 ± 5 vs 7 liters/hr; p < 0.05). Systolic and diastolic blood pressures were significantly decreased from baseline throughout the 3-month treatment period in both groups. After long-term oral administration, elderly and young patients had comparable decreases in mean blood pressure at a given drug plasma concentration. The antihypertensive effect of amlodipine is well correlated with plasma concentration and, at a given concentration, is similar in both elderly and young patients.     

Steady state pharmacokinetics of naproxen in elderly rheumatics compared with young volunteers

The elderly rheumatic patients and 7 healthy young persons received naproxen (Naprosyn, Syntex) 500 mg orally twice a day for 4 weeks. The serum concentrations were determined using mass fragmentography. After an initial 1,000-mg dose, no significant differences were found between the two groups in peak serum concentration, time to peak serum concentration, area below the serum concentration-time curve, volume of distribution, elimination half-life, or total body clearance of naproxen. At steady state, the median total through naproxen concentration was 50.5 mg/l in the elderly and 62.7 in the young (p = 0.08); the unbound concentration was 58 micrograms/l and 44 micrograms/l, respectively (p = 0.06). There was a significant inverse correlation between serum albumin and the free fraction of naproxen (R = -0.58, p = 0.01). The hepatic extraction ratio of naproxen is relatively low and it is suggested that the reduced protein binding in the elderly may conceal the age-related reduction in cellular activity. An estimated value of intrinsic clearance was reduced by 37% in the elderly patients. It is suggested to start naproxen at the lower end of its dose range in the elderly.